New insights on the cardiovascular effects of IGF-1

Abstract

Introduction: Cardiovascular (CV) disorders are steadily increasing, making them the world's most prevalent health issue. New research highlights the importance of insulin-like growth factor 1 (IGF-1) for maintaining CV health.

Methods: We searched PubMed and MEDLINE for English and non-English articles with English abstracts published between 1957 (when the first report on IGF-1 identification was published) and 2022. The top search terms were: IGF-1, cardiovascular disease, IGF-1 receptors, IGF-1 and microRNAs, therapeutic interventions with IGF-1, IGF-1 and diabetes, IGF-1 and cardiovascular disease. The search retrieved original peer-reviewed articles, which were further analyzed, focusing on the role of IGF-1 in pathophysiological conditions. We specifically focused on including the most recent findings published in the past five years.

Results: IGF-1, an anabolic growth factor, regulates cell division, proliferation, and survival. In addition to its well-known growth-promoting and metabolic effects, there is mounting evidence that IGF-1 plays a specialized role in the complex activities that underpin CV function. IGF-1 promotes cardiac development and improves cardiac output, stroke volume, contractility, and ejection fraction. Furthermore, IGF-1 mediates many growth hormones (GH) actions. IGF-1 stimulates contractility and tissue remodeling in humans to improve heart function after myocardial infarction. IGF-1 also improves the lipid profile, lowers insulin levels, increases insulin sensitivity, and promotes glucose metabolism. These findings point to the intriguing medicinal potential of IGF-1. Human studies associate low serum levels of free or total IGF-1 with an increased risk of CV and cerebrovascular illness. Extensive human trials are being conducted to investigate the therapeutic efficacy and outcomes of IGF-1-related therapy.

Discussion: We anticipate the development of novel IGF-1-related therapy with minimal side effects. This review discusses recent findings on the role of IGF-1 in the cardiovascular (CVD) system, including both normal and pathological conditions. We also discuss progress in therapeutic interventions aimed at targeting the IGF axis and provide insights into the epigenetic regulation of IGF-1 mediated by microRNAs.

Keywords: IGF-1; IGF-1 system; atherosclerosis; cardiovascular diseases; diabetes; microRNA.

Figure 1

IGF-1 system and GH/IGF-1 axis regulation. Ghrelin and GHRH stimulate pituitary secretion of GH, while somatostatin inhibits it. GH stimulates IGF1 secretion in the liver, and IGF-1 exerts negative feedback and inhibits GH secretion. GH, growth hormone; GHRH, growth hormone-releasing hormone; IGF-1, insulin-like growth factor-1; IGF-1R, insulin-like growth factor receptor-1; IGFBPs, insulin-like growth factor binding proteins; IR, insulin receptor; VSMCs, vascular smooth muscle cells. Biorender.com was used to generate part of the Figure.

Figure 2

IGF-1 signaling pathways in CV system. ERK/MAPK and PI3K/Akt represent the main pathways involved in IGF-1 signal transduction. Activation of these pathways confer multiple protective effects on the CV system, summarized in the diagram. IGFBPs, insulin-like growth factor binding proteins; IGF-1, insulin-like growth factor-1; IGF-1R, insulin-like growth factor receptor-1; RAS, rat sarcoma protein; RAF, rapidly accelerated fibrosarcoma kinase; MEK, mitogen-activated protein kinase kinase; ERK, extracellular signal-regulated kinase; IRS1, Insulin receptor substrate-1; PI3K, phosphatidylinositol-3 kinase; Akt, serine/threonine kinase (protein kinase B); mTOR, mammalian target of rapamycin; NO, nitric oxide; VSMCs, vascular smooth muscle cells; eNOS, endothelial nitric oxide synthase.