Role and mechanisms of vascular smooth muscle cell phenotypic transition in diabetic macrovascular complications

Area of Science:

• Cardiovascular Research
• Metabolic Disease
• Vascular Biology

Background:

• Diabetic macrovascular complications are a leading cause of mortality, with significant residual risk despite current treatments.
• Vascular remodeling, driven by vascular smooth muscle cell (VSMC) phenotypic transition, is central to these complications.
• The molecular mechanisms linking VSMC metabolism and mechanosensitive pathways to vascular injury are not fully understood.

Purpose of the Study:

• To systematically review metabolic reprogramming in VSMCs during diabetes and its role in vascular remodeling.
• To elucidate mechanisms of endothelial-VSMC crosstalk and VSMC phenotypic transition in atherosclerosis.
• To explore novel therapeutic strategies for diabetic macrovascular complications.

Main Methods:

• Literature review focusing on metabolic pathways, mechanosensitive signaling, and VSMC phenotypic transition in diabetes.
• Analysis of endothelial-VSMC crosstalk and atherosclerosis progression.
• Evaluation of therapeutic strategies including microRNAs, extracellular vesicles, and protein regulation.

Main Results:

• Metabolic reprogramming in VSMCs significantly impacts vascular remodeling and atherosclerosis progression.
• Precise modulation of the metabolic-mechanical coupling network in VSMCs shows potential to attenuate plaque development and improve stability.
• Endothelial-VSMC crosstalk and VSMC phenotypic plasticity are key pathological features.

Conclusions:

• Targeting the metabolic-mechanical coupling network in VSMCs offers a promising therapeutic avenue for diabetic macrovascular complications.
• Challenges in clinical translation include targeting specificity and mechanistic complexity.
• Future research should integrate multi-omics and biomimetic models for optimized therapeutic strategies.