Improving mitochondrial function in preclinical models of heart failure: therapeutic targets for future clinical therapies?

ABSTRACTIntroduction Heart failure is a complex clinical syndrome resulting from the unsuccessful compensation of symptoms of myocardial damage. Mitochondrial dysfunction is a process that occurs because of an attempt to adapt to the disruption of metabolic and energetic pathways occurring in the myocardium. This, in turn, leads to further dysfunction in cardiomyocyte processes. Currently, many therapeutic strategies have been implemented to improve mitochondrial function, but their effectiveness varies widely.Areas covered This review focuses on new models of therapeutic strategies targeting mitochondrial function in the treatment of heart failure.Expert opinion Therapeutic strategies targeting mitochondria appear to be a valuable option for treating heart failure. Currently, the greatest challenge is to develop new research models that could restore the disrupted metabolic processes in mitochondria as comprehensively as possible. Only the development of therapies that focus on improving as many dysregulated mitochondrial processes as possible in patients with heart failure will be able to bring the expected clinical improvement, along with inhibition of disease progression. Combined strategies involving the reduction of the effects of oxidative stress and mitochondrial dysfunction, appear to be a promising possibility for developing new therapies for a complex and multifactorial disease such as heart failure.KEYWORDS: Mitochondriaheart failuretherapeutic strategiestargetsheart Article highlights Improper mitochondria function is one of the main elements of heart failure.Mitochondrial reactive oxygen species are responsible for adverse changes in cell organs, which might result in the development of heart failure.Overproduction of ROS, impaired fatty acid metabolism, and, therefore, less efficient ATP production could cause apoptosis or necrosis exacerbating heart failure.An increase in AMP-activated protein kinase activity could improve function of mitochondria in cardiomyocytes.Downregulation of autophagy and mitophagy increases mitochondrial dysfunction and leads to the progression of heart failure.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis paper was not funded.