Abstract
Exercising was reported by several studies to bring great benefits to heart failure with preserved ejection fraction (HFpEF), which reduced the hospitalization and the mortality of heart failure. However, the underlying mechanism of exercising on HFpEF remains unclear. In the present study, we designed and constructed a device that can perform early passive leg movement (ePLM) in rats and further observed whether treatment of ePLM exerts protective effects on HFpEF of rats. Rats were fed with high salt feed to establish an animal model of pre-clinical diastolic dysfunction (PDD), which would eventually develop into HFpEF, and then treated rats with ePLM. We conducted several experiments to evaluate the conditions of heart and blood vessel. The results show that diastolic functions of heart and blood vessel in rats were significantly improved by treatment of ePLM. We also found that pathological injuries of heart and blood vessel were ameliorated after treatment of ePLM. Moreover, treatment of ePLM decreased the protein levels of Collagen type I, Collagen type III, MMP2, and MMP9 in heart and blood vessel, indicating that cardiac and vascular fibrosis were reduced apparently by treatment of ePLM. Further investigation suggested that treatment of ePLM probably inhibit the activation of TGF-β1/Smad3 signaling pathway as well as promote the activation of Akt/eNOS signaling pathway in high salt diet induced HFpEF. In conclusion, treatment of ePLM alleviated high salt diet induced HFpEF by inhibiting fibrosis via suppressing TGF-β1/Smad3 signaling pathway as well as activating Akt/eNOS signaling pathway, implicating treatment of ePLM as a promising novel non-pharmacological approach for HFpEF.
Highlights
Heart failure with preserved ejection fraction (HFpEF), occupied about 50% of heart failure population, was defined as a peculiar heart failure, which displays diastolic dysfunction but maintains a normal ejection fraction [1, 2]
Despite the fact that ejection fraction (EF%) and fractional shortening (FS%) as well as left ventricle internal dimensions at the end of diastole (LVID-d) displayed few differences between the two groups, we found that left ventricular posterior wall thickness at end of diastole (LVPW-d), interventricular septum thickness at end of diastole (IVS-d), maximum peak blood flow velocity at early phase of diastole/maximum peak blood flow velocity at the end of diastole (E/A) and left ventricular mass corrected (LV mass corrected) in the HS group increased significantly (P < 0.05) in contrast to the NS group
The results show that the protein levels of p-Akt and p-eNOS reduced significantly (P < 0.01) in heart tissues of the HS group and the HS+ISO group compared to the NS group, while this effect was significantly inhibited (P < 0.05) by treatment of early passive leg movement (ePLM) in the HS+ePLM group (Figures 3G–I), suggesting that Akt/eNOS signaling pathway might play an important role in the process of cardiac fibrosis
Summary
Heart failure with preserved ejection fraction (HFpEF), occupied about 50% of heart failure population, was defined as a peculiar heart failure, which displays diastolic dysfunction but maintains a normal ejection fraction [1, 2]. HFpEF is a chronic disease and deteriorates gradually with aging [3]. The Role of ePLM in HFpEF mechanisms to the disease [4, 5]. While there was no effective therapeutic methods to improve the prognosis of HFpEF to date [7]. A novel study named PARALLAX trial show that sacubitril/valsartan can ameliorate the outcome of HFpEF, but it needs more investigations to confirm the theory [8]. According to these situations, it is necessary to find new therapeutic methods for HFpEF
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