Which substance most strongly stimulates coronary smooth‑muscle cell proliferation?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 27, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Angiotensin II Most Strongly Stimulates Coronary Smooth Muscle Cell Proliferation

Angiotensin II is the primary substance that increases growth of coronary smooth muscle cells through multiple direct and indirect mechanisms, making it the most potent endogenous mitogen for vascular smooth muscle proliferation. 1

Mechanisms of Angiotensin II-Induced Smooth Muscle Proliferation

Direct Proliferative Pathways

  • Angiotensin II promotes cardiac and vascular smooth muscle cell hypertrophy directly via activation of the angiotensin II type 1 (AT1) receptor, which triggers intracellular signaling cascades that stimulate cell growth and division. 1

  • Angiotensin II activates the mitogen-activated protein kinase (MAPK) pathway, a classical signal transduction pathway that is essential for smooth muscle cell proliferation and is shared by multiple growth factors. 2

Indirect Growth Factor Stimulation

Angiotensin II functions as a master regulator by stimulating expression of multiple downstream growth factors:

  • Angiotensin II indirectly stimulates smooth muscle proliferation by upregulating platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β) and their receptors. 1

  • In cerebral artery smooth muscle cells specifically, angiotensin II stimulates proliferation through a bFGF-dependent mechanism, where synthesis and release of bFGF is essential for the proliferative response. 3

  • Angiotensin II promotes smooth muscle cell proliferation through release of heparin-binding epidermal growth factor (HB-EGF) and transactivation of the EGF-receptor pathway, with matrix metalloproteases (MMPs) playing a necessary role in this process. 4

Inflammatory and Adhesion Molecule Pathways

  • Angiotensin II stimulates expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1), which promote inflammatory cell recruitment and contribute to the proliferative vascular response. 1

Clinical Relevance in Coronary Disease

Role in Atherosclerosis and Restenosis

  • Reactive oxygen species generated by angiotensin II stimulate inflammatory mediators that activate medial smooth muscle cells, causing them to proliferate and migrate into the subintimal space, which is fundamental to atherosclerotic plaque development. 1

  • The predominant mechanism of in-stent restenosis is neointimal hyperplasia due to smooth muscle cell proliferation, and angiotensin II is a key driver of this pathological process. 1

  • Neointimal hyperplasia involves growth factors and cytokines that stimulate cellular migration and proliferation, with angiotensin II serving as a central mediator of these processes. 1

Metabolic Contributions

  • In diabetes mellitus, hyperglycemia and hyperinsulinemia accelerate atherosclerosis via vascular smooth muscle cell proliferation, with angiotensin II playing a synergistic role through activation of the local renin-angiotensin-aldosterone system (RAAS). 1

Additional Proliferative Mechanisms

  • Angiotensin II promotes neointimal thickening through arachidonic acid metabolites derived via cytochrome P450 4A, specifically 20-hydroxyeicosatetraenoic acid (20-HETE), which mediates smooth muscle proliferation in injured arteries. 5

Important Clinical Caveat

  • Mechanical injury to the arterial wall is a critical cofactor for smooth muscle proliferation—in experimental models, smooth muscle cells maintained in 30% serum showed replication rates below 0.1% per day without injury, but mechanical injury increased intimal smooth muscle replication to 60% per day, suggesting that angiotensin II's proliferative effects are amplified in the setting of vascular injury. 6

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

6
Research

The induction of smooth muscle cell proliferation in vitro using an organ culture system.

International angiology : a journal of the International Union of Angiology, 1987

Related Questions

How should shingles be treated in adults, including antiviral regimen, pain management, corticosteroids, and vaccination?
Can an elderly patient with hepatic impairment and concurrent medications affecting cardiac rhythm use low‑dose doxepin (3–6 mg) on an as‑needed basis for occasional insomnia?
What is the diagnosis and recommended treatment?
What is the most appropriate first‑line oral contraceptive for a pre‑menopausal woman with heavy abnormal uterine bleeding?
In a patient with chronic kidney disease stage 3 whose serum creatinine increased from 1.1 mg/dL to 1.8 mg/dL, what is the appropriate evaluation and management?
How should I evaluate and manage a patient with elevated hemoglobin (Hgb) and hematocrit (Hct)?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question