Blueberry Anthocyanin Prevents Cardiovascular Dysfunction Associated With Fine Particulate Matter

Objective The aim of this study was to evaluate the effects of blueberry anthocyanins on PM_2.5-induced cardiovascular dysfunction by conducting animal experiments and population intervention trial and to explore the underlying mechanisms.The results will provide scientific basis for cardiovascular dysfunction induced by PM_2.5 in China.Methods1.Population intervention trial? The prevalence and risk factors of coronary heart disease?CHD?A cross-sectional study was conducted to investigate the prevalence and risk factors of CHD among 218 elderly in nursing home of Tianjin.? Effects of freeze-dried blueberry consumption on cardiovascular dysfunction with CHD exposed to PM_2.5A total of 59 elderly CHD patients were assigned to control group?n=28?and intervened group?n=31?.The subjects in intervened group received freeze-dried blueberry 10 g/d,others received regular diet,and all subjects underwent heart rate variability analysis every week for a period of 2 months.24-h measurements of indoor PM_2.5 were determined daily at the nursing home,levels of outdoor PM_2.5 and other atmospheric pollutants were obtained from a nearby automated monitoring station.biomarkers of cardiovascular system injuries,systemic inflammation,oxidative stress were measured at pre-supplementation and pro-supplementation.2.Animal experiments? Preliminary study on acute injury of cardiovascular system in rats induced by exposure of PM_2.532 male SD rats were divided randomly into three groups?n = 8 per group?:one control group and two groups PM_2.5 exposed to at two dose?10 mg/kg,20mg/kg?.Heart rate?HR?and electrocardiograph?ECG?morphology of rats were recorded at twenty-four hours after the third exposure.The acute effects of PM_2.5was evaluated by measuring the activity of biomarkers of cardiovascular system injuries?LDH,CK,CK-MB?.?Blueberry anthocyanin-enriched attenuate PM_2.5?Induced Cardiovascular Dysfunction Blueberry anthocyanin-enriched extracts?BAE?at three doses?0.5,1.0 and2.0 g/kg?were administered by oral gavage,to rats exposed to 10 mg/kg fine particulate matter(PM_2.5)three times a week.A positive control group was exposed to PM_2.5 without BAE treatment.We analyzed hart rate?HR?,electrocardiogram?ECG?and histopathology,and biomarkers of cardiovascular system injuries?LDH,CK,CK-MB?,systemic inflammation?IL-6,IL-10,CRP?,oxidative stress?MDA,SOD?,endothelial function?ET-1,Ang-II?,and apoptosis?Bax,Bcl-2?.Results1.Population intervention trial? The prevalence and risk factors of coronary heart disease?CHD?The prevalence of CHD of the 218 subjects was 35.32%,and hypertension,hyperlipidemia were the risk factors.? Effects of freeze-dried blueberry consumption on cardiovascular dysfunction with CHD exposed to PM_2.5In the control group,substantial reduction of HRV were significantly associated with indoor PM_2.5 levels,but not in the group receiving freeze-dried blueberry.There was a 43.14% reduction in HRV-LF?95% CI,-56.94,-24.92?and 39.42% reduction in p-NN50?95% CI,-46.80,-31.02?in control group per SD of PM_2.5?80.42?g/m3?,while a 10.89% increment in HRV-LF?95% CI,-8.02,33.68?and a 0.81% reduction in p-NN50?95% CI,-7.62,6.50?in the group receiving freeze-dried blueberry per SD of PM_2.5?80.42?g/m3?.Compared with the control group,the group that received 10 g/d freeze-dried blueberry demonstrated a decrease in CK-MB activity,levels of us-CRP and MDA,an increase in IL-10 levels and SOD activity?p<0.05?.Compared with pre-intervention,serum CK,LDH and HBDH activity increased significantly and SOD activity decreased markedly?p<0.05?in control group,whereas treatment with freeze-dried blueberry markedly reduced serum us-CRP concentrations?p<0.05?.2.Animal experiments? Preliminary study on acute injury of cardiovascular system in rats induced by exposure of PM_2.5Compared with the control group,PM_2.5 exposure could induce significantly increase of CK,CK-MB and decrease of HR?p<0.05?,change ECG types.?Blueberry anthocyanin-enriched attenuate PM_2.5?Induced Cardiovascular Dysfunction. Results indicated that BAE,particularly at 1.0 g/kg,improved ECG,decreased serum CK and CK-MB in serum and heart tissue in PM_2.5-exposed rats.These changes were accompanied by an increase in IL-10 levels,SOD activity in heart tissue,and Bcl-2 protein expression,as well as a decrease in serum IL-6,MDA in serum and heart tissue,plasma ET-1 and Ang II levels and a reduction in Bax protein expression?p<0.05?.Conclusion1.Supplementation with freeze-dried blueberry prevented HRV decline and myocardial enzyme levels related to PM_2.5 exposure in the study population,may be attributed to its anti-inflammatory and antioxidant properties.2.PM_2.5-induced cardiovascular dysfunction,including mean HR decrease,cardiac enzyme activity increase,and abnormal ECG types,may be attributed to inflammatory responses,oxidative stress,endothelial dysfunction,and cardiomyocyte apoptosis.Moreover,BAE at certain doses may inhibit PM_2.5-induced cardiovascular dysfunction by anti-inflammatory and antioxidant properties,exerting positive effects on endothelial function and inhibiting apoptosis.