Abstract
Brain natriuretic peptide (BNP) treatment increases heart function and decreases heart dilation after myocardial infarction (MI). Here, we investigated whether part of the cardioprotective effect of BNP in infarcted hearts related to improved neovascularisation. Infarcted mice were treated with saline or BNP for 10 days. BNP treatment increased vascularisation and the number of endothelial cells in all areas of infarcted hearts. Endothelial cell lineage tracing showed that BNP directly stimulated the proliferation of resident endothelial cells via NPR-A binding and p38 MAP kinase activation. BNP also stimulated the proliferation of WT1+ epicardium-derived cells but only in the hypoxic area of infarcted hearts. Our results demonstrated that these immature cells have a natural capacity to differentiate into endothelial cells in infarcted hearts. BNP treatment increased their proliferation but not their differentiation capacity. We identified new roles for BNP that hold potential for new therapeutic strategies to improve recovery and clinical outcome after MI.
Highlights
Increased vascularisation supports heart recovery after ischemia
While angiogenic inhibition contributes to the development of heart failure in cardiac injury animal models, early heart reperfusion or increased angiogenesis improves cardiac function and delays the onset of heart failure in patients suffering from cardiac ischemia (Shiojima et al, 2005; Friehs et al, 2006; Tirziu et al, 2007)
No difference was detected in heart rate, cardiac output, left ventricular diastolic volume (LV Vol;d) as well as for the index of systemic vascular resistance between both groups, demonstrating that Brain natriuretic peptide (BNP) treatment had no significant effect on volumia and no peripheral vascular effect (Bielmann et al, 2015)
Summary
Increased vascularisation supports heart recovery after ischemia. The formation of new vessels in the hypoxic area restores blood flow, provides oxygen and nutriments to the surviving cells, and promotes the migration and engraftment of new cells. Angiogenesis is the main mechanism of neovascularisation in adult infarcted hearts (Manavski et al, 2018; Li et al, 2019; Ray et al, 2010). The current consensus is that after myocardial infarction (MI), angiogenesis in the infarct border zone of the heart occurs by clonal expansion of pre-existing resident endothelial cells with no EndMT mechanism (Manavski et al, 2018; Li et al, 2019; He et al, 2017). The molecular pathway involved in myocardial neovascularisation after ischemia remains unknown. Payne et al, 2019 recently demonstrated that the developmental VEGFA-MEF2 pathway, which was thought to be involved, is impaired in adult ischaemic hearts
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