Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions

Abstract

Hypertension is a global public health issue and the leading cause of premature death in humans. Despite more than a century of research, hypertension remains difficult to cure due to its complex mechanisms involving multiple interactive factors and our limited understanding of it. Hypertension is a condition that is named after its clinical features. Vascular function is a factor that affects blood pressure directly, and it is a main strategy for clinically controlling BP to regulate constriction/relaxation function of blood vessels. Vascular elasticity, caliber, and reactivity are all characteristic indicators reflecting vascular function. Blood vessels are composed of three distinct layers, out of which the endothelial cells in intima and the smooth muscle cells in media are the main performers of vascular function. The alterations in signaling pathways in these cells are the key molecular mechanisms underlying vascular dysfunction and hypertension development. In this manuscript, we will comprehensively review the signaling pathways involved in vascular function regulation and hypertension progression, including calcium pathway, NO-NOsGC-cGMP pathway, various vascular remodeling pathways and some important upstream pathways such as renin-angiotensin-aldosterone system, oxidative stress-related signaling pathway, immunity/inflammation pathway, etc. Meanwhile, we will also summarize the treatment methods of hypertension that targets vascular function regulation and discuss the possibility of these signaling pathways being applied to clinical work.

Resolvin D1 attenuates Ang II-induced hypertension in mice by inhibiting the proliferation, migration and phenotypic transformation of vascular smooth muscle cells by blocking the RhoA/mitogen-activated protein kinase pathway

“…Studies have shown that RhoA/MAPK can promote the proliferation, migration and differentiation of VSMCs during hypertension [ 11 , 17 , 18 ]. Therefore, we examined the changes in the expression of this pathway in vitro and in vivo .…”

“…Previous studies have shown that SPMs, including RvD1, can inhibit the constriction of the rat thoracic aorta and human pulmonary artery induced by the thromboxane mimetic U46619 [ 44 ]. The contractility of VSMCs is related to cytosolic Ca 2+ concentrations and the Ca 2+ sensitivity of myofilaments, and it has been well documented that the RhoA-related signaling pathway is involved in this process [ 17 , 45 ]. Therefore, RvD1 improves hypertension not only by improving the cellular function of VSMCs but also by correcting the abnormal contractility of VSMCs.…”

Recent progresses in gut microbiome mediates obstructive sleep apnea‐induced cardiovascular diseases

“…Vascular function is widely regarded as the direct cause of high blood pressure. The primary actors in vascular function are the endothelial and smooth muscle cells 75 . Numerous studies have investigated endothelial dysfunction triggered by LPS.…”

Regulatory T cells and cardiovascular diseases

“…[55] Hypertension (HP) Blood pressure is mainly controlled by blood vessels, and inflammation has been implicated in various pathological processes leading to HP. [56] In animal models of HP, increased blood pressure is linked to low Foxp3 expression, reduced numbers of Tregs, and impaired function of Tregs. [57] Angiotensin II (Ang II) upregulates the expression of monocyte chemoattractant protein-1 in the vascular system, which is well-known for its role in promoting the infiltration of various immune cells associated with HP.…”