Small GTPases and Their Role in Vascular Disease

Int J Mol Sci. 2019 Feb 20;20(4):917. doi: 10.3390/ijms20040917.

Abstract

Over eighty million people in the United States have cardiovascular disease that can affect the heart causing myocardial infarction; the carotid arteries causing stroke; and the lower extremities leading to amputation. The treatment for end-stage cardiovascular disease is surgical-either endovascular therapy with balloons and stents-or open reconstruction to reestablish blood flow. All interventions damage or destroy the protective inner lining of the blood vessel-the endothelium. An intact endothelium is essential to provide a protective; antithrombotic lining of a blood vessel. Currently; there are no agents used in the clinical setting that promote reendothelialization. This process requires migration of endothelial cells to the denuded vessel; proliferation of endothelial cells on the denuded vessel surface; and the reconstitution of the tight adherence junctions responsible for the formation of an impermeable surface. These processes are all regulated in part and are dependent on small GTPases. As important as the small GTPases are for reendothelialization, dysregulation of these molecules can result in various vascular pathologies including aneurysm formation, atherosclerosis, diabetes, angiogenesis, and hypertension. A better understanding of the role of small GTPases in endothelial cell migration is essential to the development for novel agents to treat vascular disease.

Keywords: RhoA; cdc42; migration; rac1; restenosis; small GTPases; vascular endothelium.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cell Movement
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism
  • Humans
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Multigene Family
  • Myristoylated Alanine-Rich C Kinase Substrate / genetics
  • Myristoylated Alanine-Rich C Kinase Substrate / metabolism
  • Tunica Intima / metabolism
  • Tunica Intima / pathology
  • Vascular Diseases / etiology*
  • Vascular Diseases / metabolism*
  • Vascular Diseases / pathology

Substances

  • Biomarkers
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Monomeric GTP-Binding Proteins