Vascular Extracellular Matrix Remodeling and Hypertension

Abstract

Significance: The vascular extracellular matrix (ECM) not only provides mechanical stability but also manipulates vascular cell behaviors, which are crucial for vascular function and homeostasis. ECM remodeling, which alters vascular wall mechanical properties and exposes vascular cells to bioactive molecules, is involved in the development and progression of hypertension. Recent Advances: This brief review summarized the dynamic changes in ECM components and their modification and degradation during hypertension and after antihypertensive treatment. We also discussed how alterations in the ECM amount, assembly, mechanical properties, and degradation fragment generation provide input into the pathological process of hypertension. Critical Issues: Although the relevance between ECM remodeling and hypertension has been recognized, the underlying mechanism by which ECM remodeling initiates the development of hypertension remains unclear. Therefore, the modulation of ECM remodeling on arterial stiffness and hypertension in genetically modified rodent models is summarized in this review. The circulating biomarkers based on ECM metabolism and therapeutic strategies targeting ECM disorders in hypertension are also introduced. Future Directions: Further research will provide more comprehensive understanding of ECM remodeling in hypertension by the application of matridomic and degradomic approaches. The better understanding of mechanisms underlying vascular ECM remodeling may provide novel potential therapeutic strategies for preventing and treating hypertension. Antioxid. Redox Signal. 34, 765-783.

Identification of novel proteins and mechanistic pathways associated with early-onset hypertension by deep proteomic mapping of resistance arteries

“…3 C ; Student t test comparison, p < 0.0001, t = 7.329, df = 37). Remodeling of the ECM has been associated with vascular remodeling ( 6 ). To explore this, we took advantage of our list of significantly regulated proteins and enriched for cellular components in an additional pathway analysis using ClueGO, which identified the collagen-containing extracellular matrix pathway ( Fig.…”

“…In patients with essential hypertension and the spontaneously hypertensive rat (SHR), inward eutrophic remodeling predominates ( 3 ). Several mechanisms are proposed to influence vascular remodeling in hypertension ( 4 ), including apoptosis ( 5 ), expanded extracellular matrix (ECM) ( 6 ), vascular inflammation ( 7 ), and dysfunctional endothelium ( 8 ). In addition, several contractile and dilatory mechanisms are compromised in arteries from hypertensive animals and humans, which also contribute to the development and persistence of hypertension.…”

Role of N6-methyladenosine Modification in Cardiac Remodeling

“…It is a dynamic structural change that involves alterations to numerous cellular including endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and fibroblasts and non-cellular components, which may lead to vascular stiffness. During vascular remodeling and heart failure, abnormalities in ECs and VSMCs proliferation and migration, endothelial dysfunction, inflammatory processes, and the production or breakdown of extracellular matrix components are present and predominant ( 36 , 37 ). METTL3 and FTO have been shown to be involved in the regulation of vascular or cardiac dysfunction under stress conditions ( Table 1 ).…”

Endoplasmic Reticulum-Mitochondria Contacts: A Potential Therapy Target for Cardiovascular Remodeling-Associated Diseases

“…Endoplasmic Reticulum-Mitochondria Contacts and the Pathophysiology of Vasculature Remodeling Vascular remodeling refers to the adaptive changes in structure and function that occur in response to various physiological and pathophysiological changes closely related to aging and vascular diseases (Ma et al, 2020). The concept of vascular remodeling was first proposed by Baumbach and Heistad (1992), and vascular remodeling is not only an important pathological basis for the progression of related diseases such as hypertension and atherosclerosis, but it is also the cause of the development of such diseases (Cai et al, 2021). Analyzing the process of vasculature remodeling at the cellular level is, therefore, of vital importance to more thoroughly understand the underlying mechanisms that lead to its development and elucidate new potential therapeutic targets to prevent it.…”