CASAAV Technology to Examine Regulators of Heart Failure
Cause or Effect
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Clinicians understand heart failure (HF) as a syndrome which is characterized by a cluster of symptoms and signs that are the physiological consequence of cardiac dysfunction. Patients with HF commonly experience shortness of breath, cough and wheeze, fatigue, peripheral swelling, and loss of appetite.1 By the time HF becomes clinically apparent, the changes to myocardium are already profound. A period of subclinical HF progression can occur undetected for years. During the preclinical period, cellular remodeling of cardiomyocytes occurs, but its upstream regulators are poorly understood.
Article, see p 1874
As scientists, we are challenged to distinguish key upstream cardiomyocyte regulators of early cellular remodeling from the massive changes that occur in more advanced failing muscle. When we are able to separate cause from effect in HF progression, a new generation of diagnostic and therapeutic solutions could be available. Clinical practice will improve with a better understanding of the early pathological alterations in cardiac muscle cells, which occur within otherwise grossly normal muscle.
The cardiomyocyte structures responsible for regulating intracellular calcium transients and with that both systolic and diastolic function are the t-tubule membrane invaginations and associated cardiac dyads. Scientists have recently made major strides in understanding t-tubule organization and its alteration in failing hearts.2 Key proteins involved in maintaining t-tubule structures and their microdomains have been proposed, of which the most well-characterized include JPH2 (junctophilin-2)3,4 and CAV3 (caveolin 3).5 Recently, a membrane scaffolding protein BIN1 (bridging integrator I, also known as amphiphysin II) has emerged as being responsible for t-tubule …