Vascular smooth muscle cell immune interactions drive remodeling across cardiovascular diseases

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Frontiers in Medicine Published June 7, 2026 Medically reviewed June 7, 2026 Study authors: Yuxin Wei, Yuanpeng Liao, Cong Zhang, Jiawei Guo DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Interpret VSMC-immune interactions as emerging mechanistic targets, not yet clinically actionable.

This narrative review examines the role of vascular smooth muscle cell (VSMC)-immune interactions in driving pathological vascular remodeling across several cardiovascular conditions. The authors analyze mechanisms in atherosclerosis, hypertension, aortic aneurysms and dissection, and arteritis/cardiomyopathy.

In atherosclerosis, the review focuses on metabolic reprogramming and epigenetic regulation as mechanisms underlying pathological VSMC remodeling. For hypertension, mechanosensitive mechanisms linking inflammation and contraction are emphasized. In aortic aneurysms and dissection, kinase-driven organelle stress pathways are highlighted, while microvascular dysfunction in arteritis and cardiomyopathy is linked to the secretory profile of VSMCs.

The review is purely mechanistic and does not report pooled effect sizes, clinical outcomes, or patient-level data. Limitations are not explicitly stated, but as a narrative review, the evidence is qualitative and hypothesis-generating. No safety data or practice recommendations are provided.

Clinicians should interpret these findings as early-stage mechanistic insights that may inform future therapeutic targets, but they do not yet support changes in clinical practice.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

The dynamic interplay between vascular smooth muscle cells (VSMCs) and the immune microenvironment governs vascular repair and disease progression. This review systematically elucidates this multidimensional regulatory network. We primarily dissect the molecular mechanisms driving pathological VSMC remodeling, encompassing inflammatory signaling, regulated cell death, senescence-associated DNA damage, and organelle dysfunction. Furthermore, we delineate the bidirectional crosstalk connecting VSMCs with the extracellular matrix (ECM) and tissue-infiltrating leukocytes, notably macrophages, T cells, and neutrophils. Subsequently, we evaluate how this network dictates disease-specific pathophysiology across various cardiovascular diseases. Specifically, we analyze metabolic reprogramming and epigenetic regulation in atherosclerosis (AS), mechanosensitive inflammation-contraction coupling in hypertension, and kinase-driven organelle stress in aortic aneurysms and dissection. Moreover, we examine the secretory profile of VSMCs in pulmonary arterial hypertension (PAH) and their contribution to microvascular dysfunction in arteritis and cardiomyopathy. Ultimately, we highlight emerging therapeutic strategies targeting VSMC-immune interactions and discuss future translational prospects.