Regulation of smooth muscle cells in development and vascular disease: current therapeutic strategies

Abstract

Vascular smooth muscle cells (SMCs) exhibit extensive phenotypic diversity and rapid growth during embryonic development, but maintain a quiescent, differentiated state in adult. The pathogenesis of vascular proliferative diseases involves the proliferation and migration of medial vascular SMCs into the vessel intima, possibly reinstating their embryonic gene expression programs. Multiple mitogenic stimuli induce vascular SMC proliferation through cell cycle progression. Therapeutic strategies targeting cell cycle progression and mitogenic stimuli have been developed and evaluated in animal models of atherosclerosis and vascular injury, and several clinical studies. Recent discoveries on the recruitment of vascular progenitor cells to the sites of vascular injury suggest new therapeutic potentials of progenitor cell-based therapies to accelerate re-endothelialization and prevent engraftment of SMC-lineage progenitor cells. Owing to the complex and multifactorial nature of SMC regulation, combinatorial antiproliferative approaches are likely to be used in the future in order to achieve maximal efficacy and reduce toxicity.

Keywords::

• atherosclerosis
• cell cycle inhibition
• drug-eluting stent
• excitation–transcription coupling
• neointimal hyperplasia
• phenotypic diversity
• receptor protein tyrosine kinase
• restenosis
• vascular progenitor cells
• vein-graft disease