Why the study?
The cardiac lymphatic system plays an important role in improving myocardial edema and fluid balance but has received limited research, prompting investigation into the role of LCZ696 during transverse aortic constriction-induced cardiac hypertrophy and lymphatic remodeling.
Does LCZ696 improve cardiac hypertrophy, fibrosis, and lymphatic remodeling in a transverse aortic constriction mouse model?
Does LCZ696 improve cardiac hypertrophy, fibrosis, and lymphatic remodeling in a transverse aortic constriction mouse model?
LCZ696 improves cardiac hypertrophy, fibrosis, and lymphatic remodeling in a mouse model of pressure overload-induced heart failure.
Potential lymphatic role of LCZ696 in hypertrophy merits exploration; hypothesis-generating and should not yet change practice.
Cardiac hypertrophy and ventricular remodeling following heart failure are important causes of high mortality in heart disease patients. The cardiac lymphatic system has been associated with limited research, but it plays an important role in the improvement of myocardial edema and the promotion of fluid balance. LCZ696 is a novel combination of angiotensin and neprilysin inhibitors. Here, we studied the role played by LCZ696 during transverse aortic constriction (TAC) induced cardiac hypertrophy and changes in the lymphatic system. Mice undergoing aortic coarctation were constructed to represent a cardiac hypertrophy model and then divided into random groups that either received treatment with LCZ696 (60 mg/kg/d) or no treatment. Cardiac ultrasonography was used to detect cardiac function, and hematoxylin and eosin (H&E) and Masson staining were used to detect myocardial hypertrophy and fibrosis. The proinflammatory factors interleukin‐6 (IL‐6), IL‐1 β , and tumor necrosis factor‐ α (TNF‐ α ) were detected in the blood and heart tissues of mice. The protein expression levels of lymphatic‐specific markers, such as vascular endothelial growth factor C (VEGF‐C), VEGF receptor 3 (VEGFR3), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE‐1) were detected in mouse heart tissues. We also examined the colocalization of lymphatic vessels and macrophages by immunofluorescence. The results showed that LCZ696 significantly improved heart dysfunction, cardiac hypertrophy, and fibrosis and inhibited the expression of proinflammatory factors IL‐6, IL‐1 β , and TNF‐ α in the circulating blood and heart tissues of mice. LCZ696 also decreased the protein expression levels of VEGF‐C, VEGFR3, and LYVE‐1 in mouse heart tissues, ameliorated the transport load of lymphatic vessels to macrophages, and improved the remodeling of the lymphatic system in the hypertrophic cardiomyopathy model induced by TAC.
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Ge et al. (2020) studied this question.
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