Mitochondrial Cardiomyopathy: Molecular Epidemiology, Diagnosis, Models, and Therapeutic Management

Abstract

Mitochondrial cardiomyopathy (MCM) is characterized by abnormal heart-muscle structure and function, caused by mutations in the nuclear genome or mitochondrial DNA. The heterogeneity of gene mutations and various clinical presentations in patients with cardiomyopathy make its diagnosis, molecular mechanism, and therapeutics great challenges. This review describes the molecular epidemiology of MCM and its clinical features, reviews the promising diagnostic tests applied for mitochondrial diseases and cardiomyopathies, and details the animal and cellular models used for modeling cardiomyopathy and to investigate disease pathogenesis in a controlled in vitro environment. It also discusses the emerging therapeutics tested in pre-clinical and clinical studies of cardiac regeneration.

Keywords: animal model; cellular model; diagnosis; gene therapy; mitochondrial cardiomyopathy; mitochondrial transfer/transplantation; molecular epidemiology; pharmacological approach.

Figure 1

Common complications of MCM. MCM patients can present a range of systemic multiorgan symptoms. The spectrum of tissues involved varies between the mutation (mtDNA or nDNA), heteroplasmy, and age of onset and thus makes it difficult to predict disease progression.

Figure 2

Flow chart for diagnosis of mitochondrial diseases.