The Impairment of ILK Related Angiogenesis Involved in Cardiac Maladaptation after Infarction

Abstract

BackgroundIntegrin linked kinase (ILK), as an important component of mechanical stretch sensor, can initiate cellular signaling response in the heart when cardiac preload increases. Previous work demonstrated increased ILK expression could induce angiogenesis to improved heart function after MI. However the patholo-physiological role of ILK in cardiac remodeling after MI is not clear.Method and ResultsHearts were induced to cardiac remodeling by infarction and studied in Sprague-Dawley rats. Until 4 weeks after infarction, ILK expression was increased in non-ischemic tissue in parallel with myocytes hypertrophy and compensatory cardiac function. 8 weeks later, when decompensation of heart function occurred, ILK level returned to baseline. Followed ILK alternation, vascular endothelial growth factor (VEGF) expression and phosphorylation of endothelial nitric oxide synthase (eNOS) was significantly decreased 8 weeks after MI. Histology study also showed significantly microvessel decreased and myocytes loss 8 weeks paralleled with ILK down-regualtion. While ILK expression was maintained by gene delivery, tissue angiogenesis and cardiac function was preserved during cardiac remodeling.ConclusionTemporally up-regulation of ILK level in non-ischemic myocytes by increased external load is associated with beneficial angiogenesis to maintain infarction-induced cardiac hypertrophy. When ILK expression returns to normal, this cardiac adaptive response for infarction is weaken. Understanding the ILK related mechanism of cardiac maladaptation leads to a new strategy for treatment of heart failure after infarction.

Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function

“…Both wild-type and ILK R211A genes offer potential advantages compared with SERCA-2a gene therapy 5 , based on their capacity to enhance SERCA-2a function through phosphorylation of PLN, and also to promote cardioprotection through collateral activation of prosurvival pathways 62,63 . The ILK R211A transgenic mouse is resistant to angiotensin II-induced adverse cardiac hypertrophy 15 and, moreover, is not oncogenic when overexpressed, suggesting that the ILK R211A mutant is a potentially superior gene therapy candidate.…”

Effects of nitric oxide on renal interstitial fibrosis in rats with unilateral ureteral obstruction

“…VEGF is regarded as a potent and critical angiogenic factor (Kang et al, 2001a(Kang et al, , 2001b(Kang et al, , 2001c(Kang et al, , 2001dGeerts et al, 2006;Xie et al, 2011;Vecerova et al, 2012), and eNOS works in conjunction with VEGF to promote angiogenesis (Ziche et al, 1997;Fukumura et al, 2001). Furthermore, NO has been shown to be both a downstream and upstream regulator of VEGF-mediated angiogenesis (Kimura and Esumi, 2003).…”

Integrin-Linked Kinase Controls Choroidal Neovascularization by Recruitment of Endothelial Progenitor Cells

“…Recently, ILK was found to be involved in vessel formation. 10,11 Moreover, ILK also participates in postnatal vasculogenesis by recruiting EPC to ischemic tissues 12 or by augmenting the angiogenic properties of EPC. 13 The purpose of this study was to investigate the role of ILK in CNV.…”