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Hypertension and immune system disorders

Hypertension and immune system disorders

Diskrders atherosclerosis Micronutrient fortification associated with hypovitaminosis D and angiotensin-converting Diosrders inhibitor non-use in lupus patients. Salt-responsive gut commensal modulates T H 17 axis and disease. Weng MBaron DMBloch KD et al. Yusuf S, et al.

Hypertension and immune system disorders -

Department of Immunobiology, Yale University, New Haven, Connecticut, USA. Address correspondence to: Jordan S. Pober, 10 Amistad Street, Yale University School of Medicine, New Haven, Connecticut , USA.

Phone: pober yale. Find articles by Pober, J. in: JCI PubMed Google Scholar. Published September 17, - More info. Oxidative damage and inflammation are both implicated in the genesis of hypertension; however, the mechanisms by which these stimuli promote hypertension are not fully understood.

Here, we have described a pathway in which hypertensive stimuli promote dendritic cell DC activation of T cells, ultimately leading to hypertension.

Using multiple murine models of hypertension, we determined that proteins oxidatively modified by highly reactive γ-ketoaldehydes isoketals are formed in hypertension and accumulate in DCs.

Isoketal accumulation was associated with DC production of IL-6, IL-1β, and IL and an increase in costimulatory proteins CD80 and CD Moreover, isoketal scavengers prevented these hypertension-associated events.

Plasma F2-isoprostanes, which are formed in concert with isoketals, were found to be elevated in humans with treated hypertension and were markedly elevated in patients with resistant hypertension.

Isoketal-modified proteins were also markedly elevated in circulating monocytes and DCs from humans with hypertension. Our data reveal that hypertension activates DCs, in large part by promoting the formation of isoketals, and suggest that reducing isoketals has potential as a treatment strategy for this disease.

Annet Kirabo, Vanessa Fontana, Ana P. de Faria, Roxana Loperena, Cristi L. Galindo, Jing Wu, Alfiya T. Bikineyeva, Sergey Dikalov, Liang Xiao, Wei Chen, Mohamed A. Saleh, Daniel W. Trott, Hana A. Itani, Antony Vinh, Venkataraman Amarnath, Kalyani Amarnath, Tomasz J.

Guzik, Kenneth E. Bernstein, Xiao Z. Shen, Yu Shyr, Sheau-chiann Chen, Raymond L. Mernaugh, Cheryl L. Laffer, Fernando Elijovich, Sean S. Davies, Heitor Moreno, Meena S.

Madhur, Jackson Roberts II, David G. T cells are required for significant blood pressure elevation in mouse models of hypertension.

Recent evidence suggests that the treatments that raise blood pressure in these animal models also cause oxidation within DCs, resulting in formation of isoketal adducts of self-proteins, which activate antigen-presenting functions of these cells and serve as a source of modified self-antigens.

T cells specific for these modified self-antigens then produce cytokines that promote blood pressure elevation, consistent with the idea that hypertension is an autoimmune response to altered self.

Here, I will review the new evidence for this idea put forth by Kirabo and colleagues in this issue of the JCI , identify a number of as yet unanswered questions, and discuss some of the therapeutic implications.

Therapies based on new pathogenetic insights into the development of hypertension could have significant clinical value. One possibility is that hypertension is a form of autoimmunity 3.

David Harrison and coworkers first showed in an unanticipated role for T cells in two common models of hypertension in mice 4.

Specifically, treatment either with angiotensin II or with deoxycorticosterone acetate plus NaCl DOCA-salt barely elevated blood pressure in RAG1-deficient mice, which lack T and B lymphocytes compared with WT mice; however, adoptive transfer of syngeneic T cells in RAG1-deficient animals restored treatment-induced blood pressure elevation.

The initial Harrison study linked increased blood pressure to T cell production of TNF-α, and subsequent work revealed that T cell—derived ILA is also required to sustain hypertension in animals 5. ILA targets vascular smooth muscle cells 5 — 7 , but it is not clear whether this results in hypertension.

ILA—mediated injury to the kidney is an alternative mechanism for the development of hypertension. Angiotensin II can increase cytokine production by T cells but only when the T cells are first activated by cross-linking the T cell receptor TCR for antigen with anti-CD3 monoclonal antibody 4 , a widely used experimental surrogate for antigen recognition.

If T cells are actually activated by recognition of a specific antigen in hypertensive animals, what might this antigen be? The study by Kirabo et al.

in this issue of the JCI now suggests an answer 8. To put the findings of Kirabo and colleagues into context, it is important to consider how T cells respond to antigen. Each naive T cell i. During thymic maturation, the repertoire of developing T cells is purged to eliminate both T cells that cannot recognize peptides from self-proteins bound to self-MHC and T cells that recognize peptides derived from self-proteins with high affinity.

This maturation process leaves only the T cells that react poorly to self-peptides but can recognize with higher affinity peptides derived from nonself-proteins, typically those from invading microbes that bind to self-MHC 9. However, naive T cells that recognize structurally modified peptides derived from self-proteins are not eliminated.

For example, some individuals possess T cells that recognize self-peptides in which arginine residues have been enzymatically modified to citrulline and are then displayed by the allelic forms of a specific class II MHC molecule HLA-DR4. This recognition of modified self can result in rheumatoid arthritis RA 10 , explaining why there is a much stronger risk for developing RA in individuals who have inherited an HLA-DR4 allele.

In general, a link to specific MHC alleles is a common feature of autoimmunity To initiate a T cell response, naive T cells must receive three distinct signals: specific antigen the peptide bound to the MHC molecule that is recognized by its TCR ; one or more antigen-independent boosters costimulators of T cell responses such as CD80 or CD86, which engage CD28 on the T cell ; and secreted cytokines that promote T cell expansion and differentiation Specialized antigen-presenting cells, known as DCs, provide all three signals, but DCs must first be activated in order to elicit a response from naive T cells DC-activating signals include molecules expressed by microbes, such as pathogen-associated molecular patterns PAMPs , or molecules released from injured cells, known as damage-associated molecular patterns DAMPs.

Both PAMPs and DAMPs function to localize DC activation to sites of infection or tissue injury, at which DCs acquire antigens prior to migrating to secondary lymphoid organs, in which the antigen is presented to naive T cells that express a relevant TCR.

Antigen-activated T cells proliferate, producing a clone of daughter cells specific for the relevant antigen, and these differentiate into effector cells of various types.

While there are very few naive T cells that can recognize a particular antigen, proliferation creates many effector cells that can do so. If the eliciting antigen is eliminated, most effector cells die off, but some become long-lived memory cells that can rapidly redifferentiate into new effector cells if the same antigen reappears, such as occurs during reinfection or in response to primary infection following vaccination.

This expanded pool of memory T cells is the basis of immunological memory This background provides context for the current findings of Kirabo and colleagues.

First, infusion of angiotensin II or DOCA-salt to produce hypertension generated ROS in DCs through phagocyte oxidase. Importantly, it is the mediators of hypertension, not hypertension per se, that stimulates ROS production, as normalizing blood pressure with hydralazine did not prevent ROS formation.

Second, ROS in DCs caused lipid oxidation, resulting in formation of isoketal adducts of various self-proteins. The crucial role of IFNγ—along with IL—in immune-cell mediated hypertension was previously characterized by Kamat et al. Youn et al. Once activated, these T cells remain primed to the stimulus and become easier to activate.

In a variety of models, several studies have found a dendritic cell-mediated increase in this effector memory population during hypertension — Trott et al.

The development of these populations lead to the potential for continual T cell activation and the exertion of their effects on the kidney. Expansion of T regulatory cells through low-dose IL-2 administration has been shown to lower blood pressure induced via systemic lupus erythematosus in mice; as such, these cells may play a protective role in hypertension Such a protective role may involve an immunosuppression independent mechanism; as such, further research is needed to clarify the protective, antihypertensive role of regulatory T cells in the kidney In addition to T cells, B cells have been observed to increase within- and invade- the hypertensive kidneys.

However, in mice that lack mature B cells through B-cell activating factor receptor deficiency, hypertension was attenuated in the Ang II model 8. B cells play a role in the accumulation of MPS and T cells, which may lead to the kidney pathologies observed during hypertension.

Chronic hypertension has been identified as the leading cause of congestive heart failure The progression of hypertension into cardiac dysfunction, and that of cardiac dysfunction into heart failure, is a multi-faceted progression which often involves morphological and molecular biological changes in the cardiomyocytes, alterations within the surrounding microenvironment, and physical changes to the heart.

In addition to playing a role in the perturbation of blood pressure, often through salt-sensitive inappropriate sodium handling , decades of research have shown that immune cells are partially culprit in the onset of hypertension, the progression of cardiac dysfunction to heart failure and, possibly, even the progression of hypertension to cardiac dysfunction Either hypervolemia or increased peripheral resistance increase the pumping force requirements of the heart, especially within the left ventricle , to overcome the pressure in the aorta to successfully deliver blood to the rest of the body.

This increase in pressure within the ventricle causes excessive stretching, resulting in cardiomyocyte injury and subsequent cardiac hypertrophy—a process mediated by the immune system Furthermore, immune regulation of T cells, macrophages, fibroblasts, and dendritic cells all play a role in the worsening of cardiac function in hypertension and heart failure; as such, immunological targets appear to be promising targets to increase heart health and function in treatment of heart disease Collagen deposition in cardiac fibrosis plays an important role in the maintenance of the heart.

Fibrosis functions in both maintaining homeostasis—especially within the interstitium—and in repairing physical injury that occurs. Fibrotic remodeling is a complex function that involves the secretion and deposition of connective molecules, most importantly Collagens I and III, into the interstitial and perivascular spaces.

However, excessive deposition of these connective molecules can impair cardiac function. The increased deposition of molecules within the extracellular matrix ECM stiffens the heart chambers, thereby inhibiting the heart from expanding and contracting efficiently, and, ultimately, resulting in increased cardiac stress to maintain homeostatic output.

Therefore, preventing fibrosis in heart failure remains an attractive target to help preserve cardiac function. Matrix Metalloproteinases MMPs are a family of proteins that help regulate ECM deposition and degradation, many of which are produced by macrophages and other immune cells In particular, MMP-9 has been implicated in a wide range of functions, including the degradation of ECM During cardiac dysfunction, when the fibrotic response is excessive, MMP9 is produced to chaperone the correct degradation and disposition of molecules for proper ECM development and scar formation.

However, it has been noted that the expression of MMP9 is reduced in patients with congestive heart failure , potentially indicating an impaired ability to degrade excess collagen and further highlighting the importance of extracellular matrix homeostasis.

Macrophages, originating from monocytes found in the circulation, express a variety of markers and serve a great deal of roles in innate immunity as well as mediate adaptive immune response by cross-talking with B and T cells These cells are recruited to injured or infected cells via chemokine signaling e.

Of note, cardiac-resident macrophages appear to play a more protective role against fibrosis than monocyte-derived macrophages that infiltrate the heart and promote hypertrophy, but further research is needed to clarify the distinction in responses between monocyte derived macrophages and cardiac resident There are traditionally understood to be two main macrophage phenotypes: M1 and M2 These macrophages are considered pro-inflammatory and secrete inflammatory cytokines such as IL-1β, TNF, and IL In a neonatal injured heart model, inhibition of cyclooxygenase-2 resulted in increased M1 macrophage recruitment at the wound site which may contribute to the treatment induced suppressed cardiac hypertrophy and fibrosis ; however, resolution-phase macrophages can exhibit M1 markers yet express a unique inflammatory phenotype , making the role of M1 macrophages in cardiac fibrosis unclear.

Depletion of macrophages both phenotypes has been shown to reduce cardiac remodeling in the Dahl salt-sensitive rat , but did not identify the key contributing phenotype.

In contrast to M1 macrophages, M2 macrophages are anti-inflammatory and pro-fibrotic in function; as such, the M2 phenotype may especially contribute to the fibrogenesis in hypertensive hearts. These cytokines, commonly produced by Th2 T cells, have been shown to be directly linked to the production of collagens and the onset of fibrosis , potentially through their stimulation of M2 macrophages.

Furthermore Angiotensin II and cations have been implicated in the transition of fibroblasts to myofibroblasts capable of collagen production and deposition The M2 macrophage, alone, is not capable of depositing the collagen seen in fibrosis; rather, these cells are able to promote the transition of the homeostatic fibroblasts into fibrosis-inducing myofibroblasts Macrophages, once activated at the site of injury, can recruit more macrophages and circulating fibroblasts, leading to increased inflammation and fibrosis M2 macrophages induce myofibroblast differentiation through a number of mechanisms such as the production of TGF-1β.

A recent study by Murray et al. IL, TGF-β1, and CCl2 together appeared to result in a synergistic effect in the activation of myofibroblasts. Though these results have not been explored in the heart specifically, they indicate the M2 macrophage can exacerbate organ fibrosis, which may be relevant in hypertension and heart failure through the same myofibroblastic axis.

TGF-β plays a critical role in the onset and progression of fibrosis through myofibroblast differentiation , TGF-β signals through the SMAD pathway inside of the homeostatic fibroblasts and induces the assembly of SMADs 2 and 3 into SMAD 4.

SMAD 4 and its R-Smad counterparts then form a complex in the nucleus and modify the gene expression of the fibroblast into a myofibroblast As such, TGF-β and its downstream effects are potential targets for the ablation of fibrosis in hypertension and heart failure.

When translated, TGF-β is associated with its negative regulator, the latency associated protein LAP TGF-β function can be arbitrated through multiple mechanisms, including through interaction with αVβ6, an inflammation-associated integrin expressed on epithelial cells Munger et al.

IL targets M2 macrophages and activates them to a collagen-producing, pro-fibrotic phenotype Pro-fibrotic macrophages play a critical role in the pathological progression of hypertension to diastolic dysfunction and heart failure Furthermore, it has been shown that IL deletion in a murine heart failure model attenuates erroneous fibrotic response and reduces mortality 52 , suggesting IL signaling cascades may be relevant therapeutic targets to prevent the progression of hypertension into heart failure.

Macrophages, their differentiation, and their signaling molecules present potentially valuable targets for preventing the onset of fibrosis during hypertension and heart failure outlined in Figure 2. However, the progression of fibrosis in hypertension and heart failure is not yet fully understood; as such, other pro-inflammatory immune cells may be contributing to the pathology.

In a pressure overload mouse model of heart failure through transverse aortic constriction, Wang et al.

Natural killer NK cells, on the other hand, may play a protective role via attenuating cardiac fibrosis Additional research is needed to clarify the role of other innate immune cells in hypertension induced cardiac fibrosis.

Figure 2. Macrophages and their mechanistic role in fibrosis. M2 macrophages can interact with αVβ6, thereby releasing a TGF-β inhibitor protein, and allowing them to interact with fibroblasts in the heart.

It is these myofibroblasts that are thought to account for much of the fibrotic remodeling in many diseases, including diastolic dysfunction and heart failure. These cells serve a variety of functions in response to both foreign antigens and injury.

Laroumanie et al. While preventing the aberrant increase in LOX maturation may prevent the progression of hypotrophy to heart failure, the production of LOX from pro-LOX is not fully understood and may be dependent on a number of factors, complicating the development of therapies If pro-inflammatory T cells are contributing to the development of hypertension and subsequent cardiac fibrosis, it would likely follow that regulatory T cells may play a protective effect.

Indeed, Wang et al. As previously mentioned, Laroumanie et al. In their study on immune cell activity post myocardial infarction, IIatovskaya et al. Reactive oxygen species ROS are a hallmark of many diseases, including cancer, heart disease, and other organ diseases Several potential mechanisms are available for a T cell to induce ROS release or production, such as the rupture of phagocytes that can sequester ROS Excessive ROS production due to T cell activity can negatively affect contractility within the heart, among other dysfunctions.

One such mechanism, as depicted in Figure 3 , has been identified to involve Myosin II, which relies on myosin phosphatase to be dephosphorylated, leading to the relaxation of the muscle fibers.

Myosin phosphatase is activated by protein kinase G, which, previously, had been activated by secondary messenger cGMP. This cGMP is produced by soluble Guanylate Cyclase sGC in the heart. sGC is activated by endogenous NO, which is produced by eNOS.

eNOS is known to be inhibited by increased levels of intracellular ROS; as such, downstream contractility regulated by eNOS will be negatively impacted by increased ROS By this mechanism, T cell activity in the failing heart might indirectly lead to decreased cardiomyocyte relaxation, which could further exacerbate cardiac stress and the progression to heart failure.

Therapies for eNOS inactivity exist in which sGC is stimulated by small molecules to be more reactive to decreased levels of NO Further research is needed to determine whether the ablation of T cells might have a protective role on this function of the cardiomyocytes through reducing inflammatory ROS production , Figure 3.

The outcome of ROS production on cardiomyocyte function. Soluble Guanylate Cyclase sGC drives Myosin II dephosphorylation and smooth muscle relaxation via production of the secondary messenger cGMP.

sGC is activated by intercellular NO produced by endothelial nitric oxide synthase eNOS. Reactive oxygen species inhibit eNOS activity, thereby affecting cardiomyocyte function further downstream.

sGC enhancers target sGC at an allosteric site to increase its sensitivity to NO, thereby rescuing function despite lower NO availability. Systemic administration of any drug will be expected to result in eventual off-target effects ; as such, it should be unsurprising to consider that systemic administration of antihypertensives may result in alterations of off-target organ -or cellular- functions.

Although such unintended molecule-receptor interactions are typically referred to as toxicities, it is also possible that the desired phenotype i. To this end, it can become relevant to consider if receptors targeted by antihypertensives are also expressed and functional on other cells—such as immune cells that play a critical role in the development of hypertension 31 , 35 , An excellent discussion by Felkle et al.

For the purpose of this review, we will provide a brief outline of several receptors and current understanding of expressing immune cell types and potential contributing mechanisms Figure 4. Figure 4. Immune cells known to express receptors antagonized by current antihypertensives and known change in signaling or function as a result of receptor antagonism.

The AT1 receptor, target of ARBs such as Candesartan, was described on splenocytes in , and further experiments have found this receptor on T cells , macrophages , and dendritic cells Using an [3H] thymidine incorporation assay, Nataraj et al. This link between angiotensin II and splenocyte proliferation indicated a potential for AT1 receptor antagonism to repress immune function.

Indeed, Nataraj et al. Such regulation opens the possibility of ARBs to influence immune function in addition to reducing vasoconstriction.

Likewise, antagonizing AT1R reduced numbers of dendritic cells and reduced chemokine production in an experimental model of autoimmune encephalomyelitis, indicating this receptor can contribute to dendritic cell-mediated inflammation Activated dendritic cell numbers increase in angiotensin-II induced hypertension , and Nahmod et al.

Taken together, these findings indicate ARBs may elicit some of their antihypertensive effects through direct immune-modulation in addition to blocking the vasoconstrictive effect of angiotensin II.

Further studies are needed to clarify some of these alternative mechanisms of action; however, it appears reasonable to anticipate that some of the antihypertensive effects of ARBs may be mediated through non-traditional mechanisms.

The presence of a bumetanide sensitive channel on mouse macrophages J The presence and functionality of a channel on macrophages targetable by bumetanide and resulting in attenuated activation following stimulation suggests a potential for loop diuretics to blunt macrophage involvement in the progression of hypertension.

ENaC, therapeutically targeted by mineralocorticoid receptors MR blockers such as spironolactone to reduce expression indirectly or direct blockers such as amiloride, has been suggested to be expressed on dendritic cells 39 , macrophages , and neutrophils upregulated in hypertension , playing a crucial role in regulating their involvement in hypertension.

On dendritic cells, an amiloride sensitive channel has been demonstrated to regulate NADPH oxidase production, influencing isolevuglandin-protein adduct formation, T cell recruitment, and activation These protein adducts may play a critical role in driving T cell involvement in the pathogenesis of hypertension 37 , ; as such, systemic administration of amiloride may lower blood pressure at least partially by reducing dendritic cell-to-T cell recruitment in hypertension, but further experimentation is necessary for confirmation if such an off-target mechanism is clinically relevant.

In macrophages, a similar role for amiloride sensitive channel promotion of the inflammatory response has been characterized as well, indicating that systemic administration of amiloride may reduce macrophage inflammatory responses which have been demonstrated to play a role in the progression of hypertension 36 , 86 , In like manner, antagonism of the MR receptor with Finerenone or eliminating myeloid mineralocorticoid receptor expression has been shown to reduce the pro-inflammatory macrophage population in mouse and Large White Pig models, protecting against AKI-induced chronic kidney dysfunction This correlation between myeloid MR reduction in function and reduced macrophage inflammation suggests that current mineralocorticoid receptor antagonists may partially reduce blood pressure and tissue inflammation through alteration of macrophage function within the kidneys and heart.

If such a non-classically predicted effect of antihypertensives can be verified, it would further highlight the inextricable connection between hypertension and inflammation within the kidneys and heart.

The role of catecholamines such as norepinephrine or epinephrine on these cells due to beta adrenergic stimulation varies based on cell type 1. T effector function has been modulated successfully through NE-induced reduction in dendritic cell IL12p70 secretion leading to reduced IFNγ and higher IL production in T cells following TCR stimulation by the LPS and NE exposed DCs Although many of the nuances of this regulatory relationship between β2AR signaling and cytokine production are not yet understood, it is clear that such a relationship exists 1 and may influence innate-to-adaptive immunity recruitment in pro-inflammatory situations Further research is needed to identify the effect of β-blockers on influencing the immune interactions contributing to blood pressure elevation.

L-type calcium channels LTCCs , blocked by calcium channel blockers such as amlodipine resulting in slower depolarization of vascular smooth muscle cells and conduction in the atrioventricular node , have been found expressed on macrophages , T cells , dendritic cells Cav1.

A hallmark signal of activation within immune cells involves an influx of calcium within the cytosol—either from extracellular sources or from a combination of release from intracellular stores and extracellular-to-cytosolic influx — The presence of these functional calcium channels on immune cells and their potential contribution to calcium influx lends credibility to the possibility that inhibition of LTCCs may influence immune cell proliferation and activation , Evidence has been provided clinically by -perhaps somewhat surprisingly- dentistry wherein CCBs result in increased risk of gingivitis in patients, something also associated with immunosuppression , This excellent review by Badou et al.

Upregulation of the cytokines IL and IFNγ 21 , IL-6 and TNFα 44 , and IL 18 , has been correlated with clinical manifestation of essential hypertension, among other cytokines To this end, targeting the immune system to reduce cytokine production and immune cell activation and infiltration may reduce blood pressure and subsequent tissue damage.

This excellent review by Murray et al. Further studies are needed to address the potential effectiveness of alternative immunosuppressant therapies in reducing blood pressure. Several promising pre-clinical studies have been conducted indicating the feasibility of using FDA-approved nanodrug platforms to deliver tissue specific immunosuppressant therapy minimizing off-target toxicities , but further validation and studies are required before use in a clinical setting Regardless of current difficulties, targeted immunosuppression to reduce inflammation and immune-mediated organ dysfunction in hypertension continues to be of scientific interest.

The immune system plays a role in the pathogenesis of hypertension through several inflammatory signaling mechanisms involving cells from both the innate and adaptive immune system; however, the signaling molecules and pathways governing these interactions have proven to be complex and not yet fully understood.

Within both the heart and kidney , current data suggests higher pressure can, alone, drive immune infiltration and subsequent inflammation within the invaded organ leading to dysfunction. The immune system not only contributes to blood pressure elevation 35 but also mediates organ dysfunction and dysregulation initiated by elevated blood pressure This inextricable connection between immunity, hypertension, inflammation, and organ dysfunction lends high priority to targeting the immune system to lower blood pressure or, at least, reduce inflammation due to hypertension Even current FDA approved anti-hypertensives may mediate some of their beneficial effects through immune modulation, but further studies are needed for confirmation Targeting the immune system to lower blood pressure and reduce organ damage has proven complicated , , but organ specific immune targeting using nanotechnology appears to be a promising solution to reduce toxicities , Recent identification of single nucleotide polymorphisms in SH2B adaptor protein 3 contributing to T cell involvement in hypertension and renal damage further complicates therapeutic targeting as genetic mutations may predispose certain immune cells to promote inflammation, supporting consideration of individual patient genetic predispositions when identifying driving factors of hypertension to design future treatment plans, as is becoming increasingly debated As contributing immune players and inflammation-mediating molecules are characterized, novel pathways can be identified and targeted therapeutically to lower blood pressure and attenuate hypertension-mediated organ dysfunction.

Recent studies have highlighted several such immunity-associated relevant receptors or cytokines and confirmed their relevance in several animal models of hypertension. LNB wrote the original draft and edited the manuscript; KD and CM contributed subsections to this review; YG generated figures; YL edited the manuscript; SM was responsible for the funding acquisition, provided supervision, and reviewed and edited the manuscript.

All authors contributed to the article and approved the submitted version. The content of this article reflects the personal experience and views of the author s and should not be considered medical advice or recommendation.

Responsibility for the information and views expressed herein lies entirely with the author s. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

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Hypertension, CLA and hormonal imbalances high blood pressure, is the most common ysstem disease in America. People with Hypertensioon are at risk for heart attack, Hypertension and immune system disorders, Hyperteension kidney damage. Did Hypertension and immune system disorders know that Body fat threshold is a Hypegtension between hypertension and autoimmune disease? Were you aware there are over different causal factors in hypertension? Autoimmunity is when your immune system attacks healthy cells in your body by mistake. The immune system is supposed to protect the body from infection and disease, but sometimes it breaks down and targets our own tissues. Studies have shown that people with autoimmune diseases are more likely to develop hypertension, and vice versa.

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Inflammatory Tales in Cardiovascular Medicine (Joseph A. Hill, MD) Open access peer-reviewed chapter. Hypertension and immune system disorders 26 April Reviewed: 06 May Published: Hypetrension June com ahd cbspd. Hypertension Hypeetension a widely Reducing oxidative damage Menstrual health management a major modifiable Hypertensioj factor Body fat threshold cardiovascular sisorders. Despite the available long list of anti-hypertension drugs and lifestyle modification strategies for blood pressure control, a large number of hypertensive patients fail to achieve adequate blood pressure control even when prescribed a combination of drugs from three or more classes. Thus, identifying and targeting of further mechanisms that underlie hypertension is decisive in alleviating burden of this disorder. In recent decades research have shown that perturbed immune system and inflammation contribute to hypertension. Hypertension and immune system disorders

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