Immunomodulatory Activity of Cytokines in Hypertension: A Vascular Perspective

Author:

dos Passos Rinaldo R.1ORCID,Santos Cintia V.12ORCID,Priviero Fernanda13ORCID,Briones Ana M.456ORCID,Tostes Rita C.2ORCID,Webb R. Clinton13,Bomfim Gisele F.17

Affiliation:

1. Cardiovascular Translational Research Center, School of Medicine (R.R.d.P., C.V.S., F.P., R.C.W., G.F.B.), University of South Carolina, Columbia.

2. Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil (C.V.S., R.C.T.).

3. Department of Biomedical Engineering, College of Engineering and Computing (F.P., R.C.W.), University of South Carolina, Columbia.

4. Department of Pharmacology, Facultad de Medicina, Universidad Autónoma de Madrid, Spain (A.M.B.).

5. Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, Spain (A.M.B.).

6. CIBER Cardiovascular, Madrid, Spain (A.M.B.).

7. NUPADS - Health Education and Research Center, Institute of Health Sciences, Federal University of Mato Grosso, Sinop, Brazil (G.F.B.).

Abstract

Cytokines play a crucial role in the structure and function of blood vessels in hypertension. Hypertension damages blood vessels by mechanisms linked to shear forces, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, oxidative stress, and a proinflammatory milieu that lead to the generation of neoantigens and damage-associated molecular patterns, ultimately triggering the release of numerous cytokines. Damage-associated molecular patterns are recognized by PRRs (pattern recognition receptors) and activate inflammatory mechanisms in endothelial cells, smooth muscle cells, perivascular nerves, and perivascular adipose tissue. Activated vascular cells also release cytokines and express factors that attract macrophages, dendritic cells, and lymphocytes to the blood vessels. Activated and differentiated T cells into Th1, Th17, and Th22 in secondary lymphoid organs migrate to the vessels, releasing specific cytokines that further contribute to vascular dysfunction and remodeling. This chronic inflammation alters the profile of endothelial and smooth muscle cells, making them dysfunctional. Here, we provide an overview of how cytokines contribute to hypertension by impacting the vasculature. Furthermore, we explore clinical perspectives about the modulation of cytokines as a potential therapeutic intervention to specifically target hypertension-linked vascular dysfunction.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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