Rescuing Cardiovascular Disease Caused by Tropomyosin Mutations

Cardiovascular diseases are a leading cause of death worldwide and health care expenditure. There are a variety of treatments for individuals diagnosed with cardiovascular disease depending upon the severity of symptoms, which include diet and exercise, medications, stents, and newly-developed gene therapies and drugs. The focus of this article will be on the molecular and biochemical mechanisms of how different genetic mutations in cardiac sarcomeric contractile proteins can lead to cardiomyopathic disease in mice. We will use the tropomyosin gene family and its associated proteins as a paradigm to illustrate the wide variety of clinical phenotypes that mutations in tropomyosin can impart. Potential therapeutic approaches for the rescue of cardiomyopathies, such as normalization of myofilament calcium sensitivity and introduction of chimeric genes/proteins, will be discussed as examples of “proof-of-concept” ideas. Researchers stand on the precipice of making exponential advances in the treatment of cardiovascular diseases – let us hope that we can soon take that forward step into this promising future.