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Quercetin Reverses Cardiac Systolic Dysfunction in Mice Fed with a High-Fat Diet: Role of Angiogenesis
Shasha Yu1,2, Seo Rin Kim1,3, Kai Jiang1
1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
Insights
Quercetin (Q) protects against high-fat diet (HFD) induced heart damage by improving microcirculation and reducing oxidative stress, independent of senolysis. This flavonoid offers potential cardioprotection for HFD-related cardiac issues.
Area of Science:
- Cardiovascular Research
- Nutritional Science
- Pharmacology
Background:
- High-fat diets (HFD) increase cardiometabolic syndrome and cardiac injury risk.
- Quercetin (Q) has shown cardioprotective effects, primarily linked to senolysis in ischemic models.
- The role of Q in mitigating HFD-induced cardiac damage via microcirculation restoration is unexplored.
Purpose of the Study:
- To investigate the cardioprotective effects of quercetin in a murine model of high-fat diet-induced cardiac damage.
- To determine if quercetin alleviates cardiac injury by restoring myocardial microcirculation.
- To assess the direct angiogenic potential of quercetin in vitro.
Main Methods:
- C57BL/6J mice were fed standard chow or HFD for 6 months, followed by 10 weeks of Q or vehicle treatment.
- In vivo assessment of left ventricular function via magnetic resonance imaging.
- Ex vivo analysis of intramyocardial fat, microvascular density, oxidative stress, and senescence; in vitro human umbilical vein endothelial cell (HUVEC) assays.
Main Results:
- Quercetin normalized HFD-induced increases in body weight, heart weight, and triglycerides.
- Left ventricular ejection fraction improved with Q treatment in HFD mice.
- Q prevented cardiac fat accumulation, fibrosis, cardiomyocyte hypertrophy, oxidative stress, and vascular rarefaction; no cardiac senescence was observed.
- In vitro, Q enhanced HUVEC tube formation inhibited by ox-LDL.
Conclusions:
- Quercetin exerts cardioprotective effects in HFD-fed mice, potentially through direct angiogenesis and reduced myocardial oxidative stress.
- These benefits appear independent of senolytic activity and may involve decreased plasma triglycerides and intramyocardial fat.
- Quercetin demonstrates potential as a therapeutic strategy against HFD-induced cardiac dysfunction.
Abstract:
Global consumption of high-fat diets (HFD) is associated with an increased incidence of cardiometabolic syndrome and cardiac injury, warranting identification of cardioprotective strategies. Cardioprotective effects of quercetin (Q) have mostly been evaluated in ischemic heart disease models and attributed to senolysis. We hypothesized that Q could alleviate murine cardiac damage caused by HFD by restoring the myocardial microcirculation. C57BL/6J mice were fed standard chow or HFD for 6 months and then treated with Q (50 mg/kg) or vehicle 5-day biweekly for 10 additional weeks. Left ventricular (LV) cardiac function was studied in vivo using magnetic resonance imaging, and intramyocardial fat deposition, microvascular density, oxidative stress, and senescence were analyzed ex vivo. Additionally, direct angiogenic effects of Q were studied in vitro in HUVECs. HFD increased body weight, heart weight, total cholesterol, and triglyceride levels, whereas Q normalized heart weight and triglycerides. LV ejection fraction was lower in HFD vs. control mice (56.20 ± 15.8% vs. 73.38 ± 5.04%, respectively, P < 0.05), but improved in HFD + Q mice (67.42 ± 7.50%, P < 0.05, vs. HFD). Q also prevented cardiac fat accumulation and reduced HFD-induced cardiac fibrosis, cardiomyocyte hypertrophy, oxidative stress, and vascular rarefaction. Cardiac senescence was not observed in any group. In vitro, ox-LDL reduced HUVEC tube formation activity, which Q effectively improved. Quercetin may directly induce angiogenesis and decrease myocardial oxidative stress, which might account for its cardioprotective effects in the murine HFD-fed murine heart independently from senolytic activity. Furthermore, its beneficial effects might be partly attributed to a decrease in plasma triglycerides and intramyocardial fat deposition.
