Cross-Regulation of Hypertrophic Cardiomyopathy and Pan-Apoptosis: Focusing on the Central Role of NLRC5, DRP1 and RIPK Family

Abstract

Hypertrophic cardiomyopathy (HCM) is an inherited heart disease caused directly by genetic mutations. From the molecular point of view, the pathogenesis of this disease involves a variety of pathophysiological changes, mainly including cardiac myocyte programmed death, mitochondrial dysfunction and persistent inflammatory response. Recent studies suggest that panapoptosis, a novel cell death mode, may play a key role in the development of HCM.

This article focuses on three important regulatory molecules and the potential link between hypertrophic cardiomyopathy and panapoptosis.

1. NLRC5, in HCM, showed protective effects on the heart muscle, distinct from its role in promoting cell death in other inflammatory responses.


2. DRP1, which may participate in the process of cardiomyocyte death and promote myocardial fibrosis through ZBP1-PANopsis signaling pathway. This finding reveals a potential link between mitochondrial dysfunction and pan-apoptosis.


3. RIPK family members, including RIPK1 and RIPK3. They have dual regulatory properties: on the one hand, they can promote cardiac hypertrophy through necrotic apoptosis pathway and CaMKIIδ-mPTP mechanism; on the other hand, they can integrate multiple death signals to regulate the progress of PANopsis. (Table 1)