Converting Enzyme Inhibition: Therapy for Chronic Heart Failure

Bussmann, W.‐D.

doi:10.1007/978-3-642-61627-3_21

Cited by 1 publication

(1 citation statement)

References 43 publications

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“…While generating new myocytes 31 and/or limiting cell death 32 (which we did not observe) are viable treatment options, prevailing thought is that positive inotropes are ‘whipping a sick horse to death' 33 and only used as a last resort (decompensated heart failure) 34 . We are resurrecting an ‘old idea' 1 that increasing contractility will aid a diseased heart since our approach does not have detrimental effects.…”

Section: Discussionmentioning

confidence: 68%

Rationally engineered Troponin C modulates in vivo cardiac function and performance in health and disease

et al. 2016

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Treatment for heart disease, the leading cause of death in the world, has progressed little for several decades. Here we develop a protein engineering approach to directly tune in vivo cardiac contractility by tailoring the ability of the heart to respond to the Ca2+ signal. Promisingly, our smartly formulated Ca2+-sensitizing TnC (L48Q) enhances heart function without any adverse effects that are commonly observed with positive inotropes. In a myocardial infarction (MI) model of heart failure, expression of TnC L48Q before the MI preserves cardiac function and performance. Moreover, expression of TnC L48Q after the MI therapeutically enhances cardiac function and performance, without compromising survival. We demonstrate engineering TnC can specifically and precisely modulate cardiac contractility that when combined with gene therapy can be employed as a therapeutic strategy for heart disease.

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