Part of the book: Gene Therapy Applications
Phosphorylation of cardiac sarcomeric proteins plays a major role in the regulation of physiological performance of the heart. Tropomyosin, an essential thin filament protein, regulates muscle contraction and relaxation through its interactions with actin, myosin, and the troponin complex. Studies demonstrate that changes in tropomyosin phosphorylation occur both postpartum and in response to cardiac hypertrophy and heart failure. To address the significance of tropomyosin phosphorylation on cardiac function, we conducted experiments to ascertain the effects of constitutive pseudophosphorylation, dephosphorylation, and dephosphorylation in hypertrophic cardiomyopathic hearts. Recent work demonstrates that pseudophosphorylation of tropomyosin results in dilated cardiomyopathy. Tropomyosin dephosphorylation results in a compensated or physiological cardiac hypertrophic phenotype. In addition, we demonstrated that tropomyosin dephosphorylation phenotypically rescues hearts undergoing cardiac hypertrophy. In summary, these studies collectively demonstrate a significant biological and physiological role for tropomyosin phosphorylation under both normal and cardiomyopathic conditions.
Part of the book: Cardiac Diseases and Interventions in 21st Century
In 1990, John and Christine Seidman uncovered the genetic association between mutations in sarcomeric contractile proteins and hypertrophic cardiomyopathy. Since then, the increase in knowledge and understanding of this disease has increased exponentially. Although pathologies associated with the various cardiomyopathies are vastly different, in some cases, the same proteins are causative, but with different genetic mutations. The focus of this article will be on hypertrophic and dilated cardiomyopathies, which are often caused by mutations in sarcomeric contractile proteins. Tropomyosin, a thin filament protein, serves as a paradigm to illustrate how different mutations within the same protein can generate the hypertrophic or dilated cardiomyopathic condition. As such, the significant advances in information derived from basic science investigations has led to the development of novel therapeutics in the treatment of these pathological diseases. This article will illustrate linkages which occur to bridge scientific advances to clinical treatments in cardiomyopathic patients.
Part of the book: Cardiomyopathy