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GW23-e0072
STABLE MYOCARDIAL-SPECIFIC LENTI-S100A1 GENE THERAPY RESULTS IN HEART FAILURE AFTER MYOCARDIAL INFARCTION RESCUE
  1. Wang Xuewen,
  2. Zhu zhiming
  1. Navy General Hospital

    Abstract

    Objectives The incidence of heart failure after myocardial infarction is ever-growing, and it is urgent to develop improved treatments. An attractive approach is gene therapy; however, the clinical barrier has yet to be broken because of several issues, including the lack of an ideal vector supporting safe and long-term myocardial transgene expression.

    Methods Here, we show that the use of a Lentiviral vector (Lenti-Here, we show that the use of a Lentiviral vector (Lenti-S100A1 ) containing a novel cardiac-selective enhancer/promoter element can direct stable cardiac expression of a therapeutic transgene, the calcium (Ca2+)-sensing S100A1, in a rat model of heart failure after myocardial infarction.

    Results The heart failure–rescuing properties of myocardial S100A1 expression, the result of improved sarcoplasmic reticulum Ca2+ handling, included improved contractile function and left ventricular remodelling. Adding to the clinical relevance, long-term S100A1 therapy had unique and additive beneficial effects over β-adrenergic receptor blockade, a current pharmacological heart failure unique and additive beneficial effects over treatment.

    Conclusions These findings demonstrate that stable increased expression of S100A1 in the failing heart can be used for long-term reversal of LV dysfunction and remodelling. Thus, long-term, cardiac-targeted Lenti-S100A1 gene therapy may be of potential clinical utility in human heart failure.

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