Brief CommunicationHypertension: An immune related disorder?
Introduction
Hypertension defined as chronically raised blood pressure of >140/90 mmHg is a multifactorial disorder with serious adverse outcomes including among others cardiovascular disease and chronic renal injury, posing a global threat in human health [1]. Despite the unprecedented progress in the management of hypertension over the last decades, the underlying mechanisms involved are not fully elucidated. Nevertheless, chronic inflammation and adaptive immune mechanisms are increasingly appreciated as crucial determinants [2] with immunosuppressive agents displaying antihypertensive actions [3].
Interactions between cardiac pump function, vascular resistance and regulation of blood volume by the renal system have been long recognized as the main determinants of systemic blood pressure. Though a mechanistic model between immune pathways activation and deranged physiological action of the key organ systems involved in blood pressure regulation is not entirely clear, a growing body of data supports such as link. Thus, deposition of agonistic antibodies against β1 and α1 adrenergic receptors promote acceleration of cardiac rhythm and vasoconstriction respectively. Constriction of blood vessels can be also mediated by autoantibodies against angiotensin II receptor, while IgG containing immunocomplexes can further result to heightened peripheral resistance and stiffness of the vessel wall through endothelial dysfunction, vascular remodeling and fibrosis upon ligation with Fcγ receptors on endothelial cells [4]. Finally, chronic inflammatory burden seems to also contribute to hypertension pathogenesis since increased levels of IL-6, TNF-α and soluble adhesion molecules have been associated with hypertension in apparently healthy individuals [5], while cytotoxic T lymphocytes have been shown to be activated in kidneys of hypertensive animal models [6]. To this end, integrative network analysis revealed variations of the gene encoding SH2B adaptor protein 3 – a molecule shown to modulate T cell function- to increase susceptibility to hypertension [7].
The aim of the current study was to investigate comprehensively whether aberrant humoral and cellular immune responses are implicated in hypertension.
Section snippets
Study population
The study population included 61 consecutive hypertensive patients [1] followed in the hypertension clinic of the Department of Clinical Therapeutics of “Alexandra Hospital”, National and Kapodistrian University of Athens, Athens, Greece and 55 healthy subjects of similar age/sex distribution with no history of arterial hypertension and blood pressure at entry <135/85 mmHg. Individuals with a history of autoimmune disease, recent infection or surgery (last 3 months), congestive heart failure or
Demographics, traditional risk factors and markers of subclinical atherosclerosis in hypertensive patients and healthy controls
As shown in Supplementary Table 1, significantly increased systolic and diastolic blood pressure values along with higher glucose, total cholesterol and homocysteine levels were observed in hypertensive patients compared to controls. No significant differences were detected in carotid IMT values between patients and controls. In the hypertensive group, the prevalence of diabetes was 13.1% compared to 1.8% in the control group (data not shown).
Humoral and cellular markers in hypertensive patients and controls
Immunoglobulin levels IgG, IgA and IgM and
Discussion
Though atherosclerosis has been long considered a chronic inflammatory disease with immune abnormalities playing a central role, data on the immune involvement in the setting of hypertension is rather limited. In the present study we revealed aberrations in both humoral and cellular immunity arms in hypertensive individuals compared to controls with evidence of polyclonal B cell activation expressed as an increase in serum immunoglobulins together with a reduction of T cell subpopulations in
Declration of Competing Interest
Nothing to declare
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2021, GenomicsCitation Excerpt :GO analysis of the downregulated DE RNAs showed that biological processes were significantly altered: immune response, immune system process, immune effector process, antigen processing and presentation of peptide antigen, regulation of immune system process, antigen processing and presentation, and positive regulation of immune system process. Studies have found that immune dysregulation may be a key factor in the formation of hypertension [28,29]. Autoantibodies against angiotensin II receptors can also mediate vasoconstriction [30], and immunocomplexes can further lead to increased peripheral resistance and stiffness of the vessel wall through endothelial dysfunction, vascular remodeling, and fibrosis.
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