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

Abstract

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.

Right Atrial Myocardial Remodeling in Children With Atrial Septal Defect Involves Inflammation, Growth, Fibrosis, and Apoptosis

“…The presence of IGF-1-mRNA in the RA myocardium of our patients indicates a possible protective role against fibrogenesis as it has been shown in an animal model of partial IGF-1 deficiency (34).…”

Late Health Effects of Partial Body Irradiation Injury in a Minipig Model Are Associated with Changes in Systemic and Cardiac IGF-1 Signaling

“…IGF-1 stimulates growth and development in vertebrates and maintains organ structure and homeostasis [ 80 , 81 , 82 ]. Consistent evidence from in vitro and in vivo studies have demonstrated the association between IGF-1 deficit and dysregulation of the GH/IGF-1 signaling pathways in dwarfism, arrhythmia, reduced heart contractility, inhibition of renal electrolyte reabsorption, and altered lipid metabolism, among other pathologies [ 18 , 19 , 20 , 36 , 53 ]. IGF-1 deficiency is also associated with liver and heart fibrosis [ 53 , 79 ].…”

“…Activation of the MAPK/Erk pathway determines regulation of gene expression and modulates cardiac growth, mitogenesis, and differentiation whereas activation of the Akt pathway promotes survival and inhibition of apoptosis [ 51 , 52 ]. IGF-1 deficiency has been linked to dysregulated IGF-1 signaling and oxidative stress [ 21 , 53 ]. The expressional regulation of IGF-1 is an in vivo target of peroxisome proliferator-activated receptor (PPAR) alpha transcription factor [ 54 ].…”

Impairment of IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity and Mortality

“…Changes in systemic IGF-1 and NO levels in decedent mice suggested that tissue IGF-1 signaling could be impacted by radiation-induced moribundity. Since both IGF-1 and NO signaling are important mediators of cardiovascular homeostasis [ 24 , 25 ], using SDS-PAGE/Western blot analysis, the activity of IGF-1 signaling in heart tissues of sham, irradiated survivor and decedent CD2F1 and C3H/HeN mice was evaluated. To accomplish this, the phosphorylation of the IGF-1 receptor (IGF-1R, Tyr1135/1136) that is triggered by IGF-1 ligand binding and reflects the activation of the IGF-1 signaling pathway was investigated [ 26 ].…”