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Review
. 2019 Feb 20;20(4):917.
doi: 10.3390/ijms20040917.

Small GTPases and Their Role in Vascular Disease

Alison Flentje  1 , Richa Kalsi  2 , Thomas S Monahan  3
Affiliations
Review

Small GTPases and Their Role in Vascular Disease

Alison Flentje et al. Int J Mol Sci. .

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.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Intimal hyperplasia of a vein graft at the distal anastomosis. This bypass graft was failing based on surveillance duplex ultrasound examination. (A) Arteriogram confirmed a stenosis at the distal anastomosis. (B) This patient ultimately had an open surgical revision of this anastomosis. (C) Pathology demonstrated a dense cellular lesion with a greatly thickened intima (white line) and a nearly obliterated lumen. (D) An adjacent segment of relatively normal appearing vein graft is presented for comparison (Scale bar = 100 μm).
Figure 2
Figure 2
MARCKS knockdown decreases the time to reestablishment of an intact endothelium. (A) The mouse femoral artery (B) was denuded by passage of a 0.014 inch-diameter wire. (C) At the time of euthanasia, the animal was perfused with 0.3% Evans Blue dye which stained the damaged artery. (D) A normal, intact endothelium prevents Evans Blue from binding to the basement membrane. (E) Damage to the endothelium allows Evans Blue to bind to the vessel. (F) Vessels treated with siMARCKS reestablished baseline endothelial function three days after injury. (G) Nontargeting siControl exhibited little return of endothelial function at three days (scale bars = 100 μm).
Figure 3
Figure 3
Small GTPases enzymes function. These enzymes function is controlled by (GEFs) that catalyze the exchange of GDP to guanosine triphosphate GTP activating the enzyme. It is inactivated by GTPase-activating proteins (GAPs) that stimulate GTP hydrolysis. Guanosine nucleotide dissociation inhibitors (GDIs) can act by binding to this lipid group and thus extracting them from the membrane.
See this image and copyright information in PMC

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