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Novel Immune Mechanisms in Hypertension and Cardiovascular Risk.

ABSTRACT: Hypertension is a common disorder with substantial impact on public health due to highly elevated cardiovascular risk. The mechanisms still remain unclear and treatments are not sufficient to reduce risk in majority of patients. Inflammatory mechanisms may provide an important mechanism linking hypertension and cardiovascular risk. We aim to review newly identified immune and inflammatory mechanisms of hypertension with focus on their potential therapeutic impact.In addition to the established role of the vasculature, kidneys and central nervous system in pathogenesis of hypertension, low-grade inflammation contributes to this disorder as indicated by experimental models and GWAS studies pointing to SH2B3 immune gene as top key driver of hypertension. Immune responses in hypertension are greatly driven by neoantigens generated by oxidative stress and modulated by chemokines such as RANTES, IP-10 and microRNAs including miR-21 and miR-155 with other molecules under investigation. Cells of both innate and adoptive immune system infiltrate vasculature and kidneys, affecting their function by releasing pro-inflammatory mediators and reactive oxygen species.Immune and inflammatory mechanisms of hypertension provide a link between high blood pressure and increased cardiovascular risk, and reduction of blood pressure without attention to these underlying mechanisms is not sufficient to reduce risk.

SUBMITTER: Nosalski R

PROVIDER: S-EPMC5339316 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Novel Immune Mechanisms in Hypertension and Cardiovascular Risk.

Nosalski Ryszard R McGinnigle Eilidh E Siedlinski Mateusz M Guzik Tomasz J TJ

Current cardiovascular risk reports 20170306 4

<h4>Purpose of review</h4>Hypertension is a common disorder with substantial impact on public health due to highly elevated cardiovascular risk. The mechanisms still remain unclear and treatments are not sufficient to reduce risk in majority of patients. Inflammatory mechanisms may provide an important mechanism linking hypertension and cardiovascular risk. We aim to review newly identified immune and inflammatory mechanisms of hypertension with focus on their potential therapeutic impact.<h4>Re ...[more]

PMID: 28360962

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Project description:Accumulating observations in humans and animals indicate that inflammation plays a key role in atherosclerosis development and subsequent complications. Moreover, the use of loss- or gain-of-function genetically modified, atherosclerosis-prone mice has provided strong experimental evidence for a causal role of innate and adaptive immunity in atherosclerosis and has revealed the pathogenic activity of proinflammatory cytokines, including TNF (tumor necrosis factor)-?, IL (interleukin)-1?, IL-6, and IL-18, and the atheroprotective effect of anti-inflammatory cytokines, including IL-10 and TGF-?. For the past 15 years, treatments using monoclonal antibodies specifically targeting cytokines, commonly referred as biological therapies, have transformed the treatment of chronic inflammatory diseases, such as rheumatoid arthritis or psoriasis, both conditions associated with increased cardiovascular risk. Analyzing the impact of anticytokine therapies on the cardiovascular outcomes of patients with chronic inflammatory diseases provides insight into the clinical relevance of experimental data on the role of inflammation in atherothrombotic cardiovascular diseases. CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study) provided the first evidence that targeting inflammation in humans with atherosclerosis could improve clinical outcomes. Treatment with the anti-IL-1? antibody canakinumab significantly reduced recurrent cardiovascular events in individuals with stable coronary artery disease well-treated with standard-of-care measures. Other clinical studies support the protective effects of treatment with anti-TNF-? and anti-IL-6 receptor monoclonal antibodies on cardiovascular risk. Blockade of the IL-23/IL-17 axis, however, warrants caution as a cardiovascular intervention. Targeting this pathway has improved psoriasis but may augment cardiovascular risk in certain patients. Thus, careful consideration of the cardiovascular risk profile may influence the choice of the most appropriate treatment for patients with chronic inflammatory diseases.Visual Overview: An online visual overview is available for this article.

Project description:BackgroundHistory of a hypertensive disorder of pregnancy (HDP) among women may be useful to refine atherosclerotic cardiovascular disease risk assessments. However, future risk of diverse cardiovascular conditions in asymptomatic middle-aged women with prior HDP remains unknown.ObjectivesThe purpose of this study was to examine the long-term incidence of diverse cardiovascular conditions among middle-aged women with and without prior HDP.MethodsWomen in the prospective, observational UK Biobank age 40 to 69 years who reported ≥1 live birth were included. Noninvasive arterial stiffness measurement was performed in a subset of women. Cox models were fitted to associate HDP with incident cardiovascular diseases. Causal mediation analyses estimated the contribution of conventional risk factors to observed associations.ResultsOf 220,024 women included, 2,808 (1.3%) had prior HDP. The mean age at baseline was 57.4 ± 7.8 years, and women were followed for median 7 years (interquartile range: 6.3 to 7.7 years). Women with HDP had elevated arterial stiffness indexes and greater prevalence of chronic hypertension compared with women without HDP. Overall, 7.0 versus 5.3 age-adjusted incident cardiovascular conditions occurred per 1,000 women-years for women with versus without prior HDP, respectively (p = 0.001). In analysis of time-to-first incident cardiovascular diagnosis, prior HDP was associated with a hazard ratio (HR) of 1.3 (95% CI: 1.04 to 1.60; p = 0.02). HDP was associated with greater incidence of CAD (HR: 1.8; 95% CI: 1.3 to 2.6; p < 0.001), heart failure (HR: 1.7; 95% CI: 1.04 to 2.60; p = 0.03), aortic stenosis (HR: 2.9; 95% CI: 1.5 to 5.4; p < 0.001), and mitral regurgitation (HR: 5.0; 95% CI: 1.5 to 17.1; p = 0.01). In causal mediation analyses, chronic hypertension explained 64% of HDP's association with CAD and 49% of HDP's association with heart failure.ConclusionsHypertensive disorders of pregnancy are associated with accelerated cardiovascular aging and more diverse cardiovascular conditions than previously appreciated, including valvular heart disease. Cardiovascular risk after HDP is largely but incompletely mediated by development of chronic hypertension.

Dataset Information

Novel Immune Mechanisms in Hypertension and Cardiovascular Risk.

Publications

Novel Immune Mechanisms in Hypertension and Cardiovascular Risk.

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