Left ventricular pressure overload in pigs increased LV stiffness by over 40% and altered 30 microRNAs, 11 of which correlated to LV stiffness and mapped to fibrosis and calcium handling.
Does left ventricular pressure overload (LVPO) alter posttranscriptional regulation (microRNAs) in a pig model of HFpEF?
In a pig model of HFpEF, left ventricular pressure overload alters specific microRNAs that correlate with LV stiffness and map to fibrosis and calcium handling pathways.
Absolute Event Rate: 0% vs 0%
Left ventricular pressure overload (LVPO) can lead to heart failure with a preserved ejection fraction (HFpEF) and LV chamber stiffness (LV Kc) is a hallmark. This project tested the hypothesis that the development of HFpEF due to an LVPO stimulus will alter posttranscriptional regulation, specifically microRNAs (miRs). LVPO was induced in pigs (n = 9) by sequential ascending aortic cuff and age- and weight-matched pigs (n = 6) served as controls. LV function was measured by echocardiography and LV Kc by speckle tracking. LV myocardial miRs were quantified using an 84-miR array. Treadmill testing and natriuretic peptide-A (NPPA) mRNA levels in controls and LVPO were performed (n = 10, n = 9, respectively). LV samples from LVPO and controls (n = 6, respectively) were subjected to RNA sequencing. LV mass and Kc increased by over 40% with LVPO (P < 0.05). A total of 30 miRs shifted with LVPO of which 11 miRs correlated to LV Kc (P < 0.05) that mapped to functional domains relevant to Kc such as fibrosis and calcium handling. LVPO resulted in reduced exercise tolerance (oxygen saturation, respiratory effort) and NPPA mRNA levels increased by fourfold (P < 0.05). RNA analysis identified several genes that mapped to specific miRs that were altered with LVPO. In conclusion, a specific set of miRs are changed in a large animal model consistent with the HFpEF phenotype, were related to LV stiffness properties, and several miRs mapped to molecular pathways that may hold relevance in terms of prognosis and therapeutic targets.
Samani et al. (Fri,) reported a other. Left ventricular pressure overload in pigs increased LV stiffness by over 40% and altered 30 microRNAs, 11 of which correlated to LV stiffness and mapped to fibrosis and calcium handling.