IGF-1 and cardiovascular disease

Abstract

Atherosclerosis is an inflammatory arterial pathogenic condition, which leads to ischemic cardiovascular diseases, such as coronary artery disease and myocardial infarction, stroke, and peripheral arterial disease. Atherosclerosis is a multifactorial disorder and its pathophysiology is highly complex. Changes in expression of multiple genes coupled with environmental and lifestyle factors initiate cascades of adverse events involving multiple types of cells (e.g. vascular endothelial cells, smooth muscle cells, and macrophages). IGF-1 is a pleiotropic factor, which is found in the circulation (endocrine IGF-1) and is also produced locally in arteries (endothelial cells and smooth muscle cells). IGF-1 exerts a variety of effects on these cell types in the context of the pathogenesis of atherosclerosis. In fact, there is an increasing body of evidence suggesting that IGF-1 has beneficial effects on the biology of atherosclerosis. This review will discuss recent findings relating to clinical investigations on the relation between IGF-1 and cardiovascular disease and basic research using animal models of atherosclerosis that have elucidated some of the mechanisms underlying atheroprotective effects of IGF-1.

Insulin-Like Growth Factor I Prevents Cellular Aging via Activation of Mitophagy

“…Our working hypothesis is that IGF-1 induces replenishing of P20 cells via mitophagy-mediated clearance of mitochondria and suppressing of cell senescence. This hypothesis is consistent with literature data indicating prosurvival and mitogenic effects of IGF-1 [ 6 , 40 , 41 ].…”

“…It has been reported that either induction of cell senescence or interruption of autophagic signaling in vascular SMC promoted atherosclerosis and induced features of plaque vulnerability in a murine model [ 50 , 51 ]. We and others [ 40 , 41 , 52 ] have reported that IGF-1 exerts antiatherosclerotic effects in mice that are mediated (at least in part) by IGF-1 receptor-dependent SMC signaling [ 15 ]. The results of the current report suggest that the ability of IGF-1 to reduce cell senescence and activate autophagy in vascular SMC could be a novel mechanism(s) potentially contributing to IGF-1's antiatherosclerotic effects.…”

Islet Macrophages Shift to a Reparative State following Pancreatic Beta-Cell Death and Are a Major Source of Islet Insulin-like Growth Factor-1

“…IGF-1 has long been known to have a beneficial role in diabetes and cardiovascular disease (Higashi et al, 2019). Beta-cell IGF-1 overexpression protects from STZ-induced diabetes (George et al, 2002;Robertson et al, 2008) and exogenous IGF-1 protects NOD mice from developing type 1 diabetes, likely via effects on T cells (Bergerot et al, 1995;Kaino et al, 1996).…”

Considering the Role of Murine Double Minute 2 in the Cardiovascular System?

“…The studies presented above, while not exhaustive, serve as examples to highlight the diverse role of MDM2 as a central hub in the cardiovascular system. Most human cardiovascular diseases are associated with DNA damage due to oxidative stress (Jackson and Bartek, 2009;Shimizu et al, 2014;Uryga et al, 2016) and alteration of hormonal signals (Higashi et al, 2019). The DNA damage kinase ATM is an upstream regulator of MDM2, and it does modulate the endothelial function, playing a role in atherosclerosis and angiogenesis.…”