A Critical Contribution of Cardiac Myofibroblasts in Right Ventricular Failure and the Role of UCP2 SNPs in the Predisposition to RV Decompensation in Pulmonary Arterial Hypertension - PubMed
4 days ago
- #UCP2 SNP
- #Pulmonary Arterial Hypertension
- #Right Ventricular Failure
- Right ventricular failure (RVF) is a major cause of morbidity and mortality in pulmonary arterial hypertension (PAH).
- The transition from compensated right ventricle (cRV) to decompensated RV (dRV) is poorly understood, with some PAH patients progressing faster than others.
- Cardiac myofibroblasts (cMFBs) play a critical role in RV decompensation, as shown in rat models (monocrotaline and pulmonary artery banding) and human PAH cohorts.
- Loss of UCP2 (uncoupling protein 2), which regulates mitochondrial calcium (mCa++) and fibroblast differentiation, is associated with dRV.
- A loss-of-function UCP2 SNP (rs659366) may predict dRV in human PAH patients.
- Increased cMFBs and decreased UCP2 levels were observed in dRV compared to cRV in PAH patients.
- TNF-α reduces UCP2 expression in cardiac fibroblasts (cFBs), contributing to RV decompensation.
- UCP2 SNP rs659366 and lower UCP2 levels correlate with worse RV function in PAH patients.
- The study suggests cFBs-to-cMFBs transformation as a key driver of RV failure, with TNF-α and UCP2 SNPs as potential biomarkers.