Biology subjects

Koopmans, T.

Publications and source records attributed to Koopmans, T..

2 recordsLinked to original sources

bioRxiv2025

PKP2 orchestrates OXPHOS expression in cardiomyocytes via a PGC1α-dependent mechanism

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease where the majority of ACM patients carry a (likely) pathogenic variant in desmosomal genes, predominantly in plakophilin-2 (PKP2). While the genetic cause of the disease is well studied, the molecular disease-driving mechanisms and how exercise can drive disease progression remain poorly understood. In this study, we identified the oxidative phosphorylation (OXPHOS) pathway to be downregulated in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and human explanted hearts carrying pathogenic PKP2 variants. The reduced expression of OXPHOS related genes was a result of lower PPARGC1A expression which led to decreased mitochondrial spare capacity in PKP2 mutant hiPSC-CMs. Induction of PPARGC1A expression partially restored the expression of OXPHOS components and improved contractility in PKP2 mutant cells. These results suggest that improving oxidative capacity through modulation of PPARGC1A in cardiomyocytes could be considered as a new therapeutic target for ACM patients in the future.

molecular biology↗

bioRxiv2021

Ischemic tolerance and cardiac repair in the African spiny mouse

Ischemic heart disease and by extension myocardial infarction is the primary cause of death worldwide, necessitating regenerative therapies to restore heart function. Current models of heart regeneration are restricted in that they are not of adult mammalian origin, precluding the study of class-specific traits that have emerged throughout evolution, and reducing translatability of research findings to humans. Here, we overcome those restrictions by introducing the African spiny mouse (Acomys spp.), a murid rodent that has recently been found to exhibit bona fide regeneration of the back skin and ear pinna. We show that spiny mice exhibit tolerance to myocardial infarction through superior survivability, improved ventricular conduction, smaller scar size, and near-absence of cardiac remodeling. Critically, spiny mice display increased vascularization and cardiomyocyte expansion, with an associated improvement in heart function. These findings present new avenues for mammalian heart research by leveraging unique tissue properties of the spiny mouse.

developmental biology↗