Cardiorenal protective actions of a novel natriuretic peptide in both systolic and diastolic heart failure
Congestive heart failure (CHF) is a poorly managed disease with a dismal prognosis and is associated with a loss of contractility, i.e. systolic dysfunction (HF with reduced ejection fraction, HFrEF), or a preserved ejection fraction (HFpEF) but with increased stiffness or diastolic dysfunction. The broad objective of the current protocol is to advance the current knowledge on the role of the cardiorenal and humoral system in the evolution of CHF, and to advance potential new therapeutic options. Based on preliminary findings, this proposal will investigate the therapeutic effects of exogenous supplementation of a naturally produced cardiac hormone with distinctive cardiorenal and systemic protective actions in clinically relevant animal models of progressive CHF: (1) a post ischemic model of HFrEF induced by permanent ligation of the left coronary artery and acute myocardial infarction (MI), and (2) a hypertension-related model of HFpEF.
We will test the hypothesis that Drug Y preserves cardiac and renal function of HFpEF (i.e. ZSF1 rat) and HFrEF (i.e. post MI) rats. Our study will be the first aimed at investigating the effects of this hormone in HFpEF/HFrEF. Due to a distinct pharmacological profile, its beneficial effects will be amplified by combing Drug Y with a recently approved heart failure medication (Valsartan/Sacubitril, Entresto®). We anticipate that the beneficial effects of proANP31–67 (Vastiras®)(i.e. renal enhancing properties, kaliuretic effects, diuretic and natriuretic actions, systolic/diastolic functions, cardiac remodeling, etc.) will manifest in our HFpEF rat models and attenuate the deleterious effects of high blood pressure on the cardiac and renal structure and function. We expect that our studies can extend the clinical therapeutic use of this naturally occurring hormone while opening new opportunities of treatment for serious cardiovascular diseases such as evolving CHF in the setting of diastolic dysfunction, coronary artery disease, and chronic kidney disease, all conditions of high clinical relevance and priority.
We will test the hypothesis that Drug Y preserves cardiac and renal function of HFpEF (i.e. ZSF1 rat) and HFrEF (i.e. post MI) rats. Our study will be the first aimed at investigating the effects of this hormone in HFpEF/HFrEF. Due to a distinct pharmacological profile, its beneficial effects will be amplified by combing Drug Y with a recently approved heart failure medication (Valsartan/Sacubitril, Entresto®). We anticipate that the beneficial effects of proANP31–67 (Vastiras®)(i.e. renal enhancing properties, kaliuretic effects, diuretic and natriuretic actions, systolic/diastolic functions, cardiac remodeling, etc.) will manifest in our HFpEF rat models and attenuate the deleterious effects of high blood pressure on the cardiac and renal structure and function. We expect that our studies can extend the clinical therapeutic use of this naturally occurring hormone while opening new opportunities of treatment for serious cardiovascular diseases such as evolving CHF in the setting of diastolic dysfunction, coronary artery disease, and chronic kidney disease, all conditions of high clinical relevance and priority.