Neuro-endocrine immune networks leading to HIV-associated cardiovascular abnormalities: Role of leptin

Abstract

a b s t r a c tPatients infected with human immunodeficiency virus exhibit many risk factors like atherosclerosis, endothelial dysfunction and hypertension for cardiovascular disease. As the homeostatic mechanisms in body are regulated by the integrated actions of cytokines and hormones, the normal function of a human heart is also governed by the neuro-endocrine immune interactions. Patients suffering from acquired immunodeficiency syndrome manifest alterations in the neural immune networks mediated by human immunodeficiency virus and leptin, which incline them to suffer from congestive heart failure. Networks that disrupt the cardiovascular functions are the focus of this review.

Characteristics of hypertension among people living with HIV in Ghana: Impact of new hypertension guideline

“…Plasma concentrations of adiponectin, a potent vasodilator through elaboration of endothelial nitric oxide, has been shown to be significantly lower among PLWH with metabolic syndrome . Furthermore, it has been shown that PLWH on cART have higher circulating levels of leptin, which acting via leptin receptors simultaneously trigger activation of both the renin‐angiotensin‐aldosterone pathway and the sympathetic nervous system …”

Hypertension in HIV-Infected Adults

“…The pathophysiologic mechanisms by which HIV-related dyslipidemias induce hypertension are likely related to the adipocytokines adiponectin and leptin. 77,78,79,80,81 Adiponectin, an adipose tissue-derived cytokine or “adipokine”, acts as a vasodilator by stimulating endothelial nitric oxide, 77,78,80 and thus its deficiency has been shown to be critical in the pathogenesis of obesity-related hypertension in the general population. 77 In the context of HIV infection, decreased plasma levels of adiponectin have similarly been associated with metabolic syndrome.…”

“…Leptin, an adipokine generated by inflammatory cascades that are also activated in HIV infection, acts primarily on the aorta and hypothalamus. 77,81 HIV-infected individuals on ART have been shown to have elevated leptin concentrations irrespective of BMI. 82 In the aorta and hypothalamus, leptin receptors trigger the activation of both the RAAS and the sympathetic nervous system.…”

“…82 In the aorta and hypothalamus, leptin receptors trigger the activation of both the RAAS and the sympathetic nervous system. 77,81 In a family-based association analysis of the leptin gene among 695 individuals from 82 families, several single nucleotide polymorphisms (SNPs) that were significantly associated with higher plasma leptin concentrations were also associated with hypertension in women (β=0.48; 95% CI: 0.25-0.72; P <0.001), but not in men. 83 Several mechanisms may explain the association between elevated leptin and hypertension.…”

“…77,84 In addition, elevated leptin activates the sympathetic nervous system. 81,83 Leptin also activates the RAAS and the central nervous system through direct effects on the medulla oblongata and by inducing production of acute phase reactants from the liver. 81,85…”