Targeting the immune system to treat hypertension: where are we?

  title={Targeting the immune system to treat hypertension: where are we?},
  author={Jennifer L. Gooch and Avadhesh C. Sharma},
  journal={Current Opinion in Nephrology and Hypertension},
Purpose of reviewResearch over the past decade has significantly deepened our understanding of mechanisms that drive the development of hypertension. In particular, a novel paradigm of inflammation as a common mediator of cardiovascular and kidney disease has emerged. This review will summarize the role of the immune system in cardiovascular disease, explore some of the most promising new therapeutic directions and consider their potential as new treatments for hypertension. Recent… 

Neuroinflammatory mechanisms of hypertension: potential therapeutic implications

PVN and BBB seem to be pivotal targets for therapeutic intervention in hypertension, and Ang II type I receptor blockers and AngII-converting enzyme inhibitors are the most likely candidates for controlled randomized trials in humans aimed at amelioration of brain inflammation in the forthcoming years.

Interactions of hyperhomocysteinemia and T cell immunity in causation of hypertension.

It is proposed that there is a need for evaluation of the causes of HHcy, defective remethylation or defective transsulfuration, which may differentially modulate hypertension progression, not just the homocysteine levels.

Sodium nitroprusside alleviates hypertension mediated inflammation through down-regulating the expression of Cx40 in peripheral blood T lymphocytes from spontaneously hypertensive rats

Exogenous NO alleviates hypertension-mediated inflammation, which is at least partly due to the regulation of adaptive immune responses by Cx40 expression inhibition, and had a more pro-inflammatory peripheral immune profile than WKY.

Up-regulation of gap junction in peripheral blood T lymphocytes contributes to the inflammatory response in essential hypertension

The data suggest that Cx40/Cx43-based channels in lymphocytes may be involved in the regulation of T lymphocyte proliferation and the production of pro-inflammatory cytokines, which contribute to the hypertensive inflammatory response.

Systemic administration of pentoxifylline attenuates the development of hypertension in renovascular hypertensive rats

It is suggested that inflammation plays a role in renovascular hypertension and that PTX might act both peripherally and centrally to prevent hypertension.

Renin, Genes, MicroRNAs, and Renal Mechanisms Involved in Hypertension

The involvement of an intrarenal renin–angiotensin system now seems to be an important component of the pathophysiological mechanisms involved in essential hypertension.

Antiglycation Activities and Common Mechanisms Mediating Vasculoprotective Effect of Quercetin and Chrysin in Metabolic Syndrome

Q and CH provide protection against vascular dysfunction in MetS by interfering with AGEs formations and AGES-associated vascular deterioration, with CH being largely dependent on NO-mediated mechanisms of vasodilation.

Rhabdomyolysis among Critically Ill Combat Casualties: Long-Term Outcomes

The long-term outcomes of rhabdomyolysis, including mortality, renal function, and incidence of hypertension (HTN), among service members initially admitted to the intensive care unit after sustaining a combat injury in Iraq or Afghanistan between February 1- 2002 and February 1, 2011 were identified.



The immune system in hypertension.

A working hypothesis is proposed linking the sympathetic nervous system, immune cells, production of cytokines, and, ultimately, vascular and renal dysfunction, leading to the augmentation of hypertension.

Flurry of deal-making surrounds new autoimmunity target

By modulating the activity of a protein called retinoic acid– related orphan receptor-gamma t (RORgt), scientists have discovered they can prevent the differentiation of TH17 cells from T cell precursors in the thymus, leading to a flurry of activity among large drug companies seeking to add RORgt research programs to their portfolios.

Steroid diabetes: from mechanism to treatment?

An up-to-date overview of the current insights regarding the mechanisms responsible for the adverse metabolic effects of GCs that may lead to steroid diabetes is provided, particularly, on GC-related induction of insulin resistance and pancreatic islet-cell dysfunction.

The role of immune cells infiltrating the kidney in the pathogenesis of salt-sensitive hypertension.

Recent evidence that suggests that renal infiltration with immune cells plays a role in the pathogenesis of salt-sensitive hypertension is summarized to suggest potential mechanisms by which the immune infiltrate could induce or worsen salt-driven hypertension.

Mycophenolate mofetil treatment improves hypertension in patients with psoriasis and rheumatoid arthritis.

Data from patients treated with mycophenolate mofetil for the treatment of psoriasis or rheumatoid arthritis and grade I essential hypertension and normal renal function are consistent with the hypothesis that renal immune cell infiltration and oxidative stress play a role in human hypertension.

Lymphocyte responses exacerbate angiotensin II-dependent hypertension.

The absence of lymphocyte activity protects from hypertension by allowing blood pressure-induced sodium excretion, possibly via stimulation of eNOS- and COX-2-dependent pathways.

Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunction

A previously undefined role for T cells in the genesis of hypertension is identified and a role of inflammation in the basis of this prevalent disease isSupporting a novel therapeutic target for the treatment of high blood pressure.

Interleukin 17 Promotes Angiotensin II–Induced Hypertension and Vascular Dysfunction

It is concluded that IL-17 is critical for the maintenance of angiotensin II–induced hypertension and vascular dysfunction and might be a therapeutic target for this widespread disease.

An emerging role for calcineurin Aalpha in the development and function of the kidney.

  • J. Gooch
  • Biology, Medicine
    American journal of physiology. Renal physiology
  • 2006
It is intriguing to consider that while the beta-isoform may be responsible for calcineurin action in T cells, the alpha-isoforms may be the predominant catalytic isoform in the kidney, and this conclusion, if correct, may have substantial clinical implication for novel strategies to selectively target calcineURin action on T cells without associated nephrotoxicity.

Interleukin 6 Underlies Angiotensin II–Induced Hypertension and Chronic Renal Damage

Both the mouse and human studies reported here provide evidence that angiotensin II induces IL-6 production in the kidney, and that, in addition to its role in hypertension, increased IL- 6 may play an important pathogenic role in CKD by inducing fibrotic gene expression and ET-1 gene expression.