Role of the Renin–Angiotensin System in the Pathogenesis of Intimal Hyperplasia: Therapeutic Potential for Prevention of Vein Graft Failure?

Abstract

The saphenous vein remains the most widely used conduit for peripheral and coronary revascularization despite a high rate of vein graft failure. The most common cause of vein graft failure is intimal hyperplasia. No agents have been proven to be successful for the prevention of intimal hyperplasia in human subjects. The rennin–angiotensin system is essential in the regulation of vascular tone and blood pressure in physiologic conditions. However, this system mediates cardiovascular remodeling in pathophysiologic states. Angiotensin II is becoming increasingly recognized as a potential mediator of intimal hyperplasia. Drugs modulating the renin–angiotensin system include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These drugs are powerful inhibitors of atherosclerosis and cardiovascular remodeling, and they are first-line agents for management of several medical conditions based on class I evidence that they delay progression of cardiovascular disease and improve survival. Several experimental models have demonstrated that these agents are capable of inhibiting intimal hyperplasia. However, there are no data supporting their role in prevention of intimal hyperplasia in patients with vein grafts. This review summarizes the physiology of the rennin–angiotensin system, the role of angiotensin II in the pathogenesis of cardiovascular remodeling, the medical indications for these agents, and the experimental data supporting an important role of the rennin–angiotensin system in the pathogenesis of intimal hyperplasia.

Use of Plasma Renin Activity to Monitor Mineralocorticoid Treatment in Dogs with Primary Hypoadrenocorticism: Desoxycorticosterone Versus Fludrocortisone

“…Increased renin activity leads to enhanced production of angiotensin I and angiotensin II. Angiotensins have important effects on vascular endothelium and vascular smooth muscle (eg, vasoconstriction, vascular smooth muscle cell proliferation, and atherosclerosis) . In humans, PRA (or more precisely angiotensin II) is a well known cardiovascular risk factor .…”

Angiotensin II, as well as 5-hydroxytriptamine, is a potent vasospasm inducer of saphenous vein graft for coronary artery bypass grafting in patients with diabetes mellitus

“…Insulin resistance, a well-known risk factor for type 2 DM, upregulates the renin-angiotensin-aldosterone system (RAAS), which is involved in the pathogenesis of hypertension, arteriosclerosis, and ischemic heart failure [8] , [9] . Angiotensin II (AngII) is part of the RAAS and plays important roles in regulating the vascular tone and the pathogenesis of cardiovascular diseases [10] . AngII acts primarily through the angiotensin AT 1 receptor (AT 1 R) to exert the most of its biological effects, including the constriction of vascular smooth muscle.…”

Dysfunction of the arteriovenous fistula for hemodialysis as a consequence of venous neointimal hyperplasia and treatment strategies

“…There is some experience regarding the impact of ACE inhibitors on the incidence of intimal hyperplasia in patients with cardiovascular pathology [26]. Research on hemodialysis patients suggests that inhibiting the enzyme ACE may block proliferation of smooth-muscle cells as an important factor in the prevention of vascular access stenosis [27].…”