Insulin-Like Growth Factor 1 in the Cardiovascular System.

Non-communicable diseases, such as cardiovascular diseases, are the leading cause of mortality worldwide. For this reason, a tremendous effort is being made worldwide to effectively circumvent these afflictions, where insulin-like growth factor 1 (IGF1) is being proposed both as a marker and as a central cornerstone in these diseases, making it an interesting molecule to focus on. Firstly, at the initiation of metabolic deregulation by overfeeding, IGF1 is decreased/inhibited. Secondly, such deficiency seems to be intimately related to the onset of MetS and establishment of vascular derangements leading to atherosclerosis and finally playing a definitive part in cerebrovascular and myocardial accidents, where IGF1 deficiency seems to render these organs vulnerable to oxidative and apoptotic/necrotic damage. Several human cohort correlations together with basic/translational experimental data seem to confirm deep IGF1 implication, albeit with controversy, which might, in part, be given by experimental design leading to blurred result interpretation.

Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins.

Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions.