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AHA Proposal Final Marisa 2021.docx (9.16 MB)
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AHA Proposal Final Marisa 2021.docx

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posted on 2023-01-12, 03:50 authored by Sepulveda Marisa

Acute myocardial infarction (AMI) causes cardiac cell death, reduced myocardial capillary density, and subsequent scar formation. Cardiac damage due to AMI is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally downregulate target genes. Previous studies revealed fundamental impacts of miRs on cardiovascular function in humans. Intriguingly, novel miR therapies are being used in clinical trials for other diseases and more recently for heart failure (HF). We have focused on miR-532-5p (hereinafter referred to as miR-532), which is upregulated β-adrenergic receptor (βAR) antagonist [β-blocker] carvedilol (Carv) acting through β-arrestin-biased β2AR signaling. We reported for the first time that miR-532 plays a vital cardioprotective role in AMI and represses protease serine 23 (prss23). Interestingly, miR-532 expression is significantly enriched in cardiac endothelial cells (CECs) and selectively downregulated in CECs isolated from ischemic myocardium, which is inversely associated with the expression of prss2315. Despite the correlative relationship between prss23 and miR-532, their in vivo functional relationship has never been established, and mechanisms that regulate cell-specific prss23 or miR-532 expression and function in HF are unknown.


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    American Heart Association