Vascular Smooth Muscle Cell Dysfunction in Cerebral Small Vessel Disease: Mechanisms and Therapeutic Potential.

Abstract

Background: Cerebral small vessel disease (CSVD) is closely linked to stroke and dementia, marked by structural and functional impairments of small blood vessels in the brain.

Summary: This review focuses on how vascular smooth muscle cells (SMCs) contribute to CSVD progression. SMCs regulate cerebral blood flow, maintain vascular structure, and support glymphatic waste clearance under physiological conditions. However, in the context of CSVD, these cells undergo pathological alterations, such as hypertrophy, degeneration, phenotypic switching, and extracellular matrix abnormalities. These dysregulations are associated with malfunctions in multiple signaling pathways or disrupted mechanical cellular responses. Emerging treatments, such as drugs targeting cyclic nucleotide pathways, show promise in improving blood flow and vascular stability.

Key messages: Despite progress, the molecular mechanisms underlying SMC dysfunction in CSVD remain incompletely understood. A deeper exploration of SMC biology, coupled with clinical translation of preclinical findings, is critical for developing effective therapies to address the escalating burden of CSVD.