Aging is an independent risk factor for cardiovascular diseases.Cardiac diastolic dysfunction(CDD),ultimately leading to heart failure with preserved ejection fraction(HFpEF),is prevalent among older individuals.Altho...Aging is an independent risk factor for cardiovascular diseases.Cardiac diastolic dysfunction(CDD),ultimately leading to heart failure with preserved ejection fraction(HFpEF),is prevalent among older individuals.Although therapeutics have made great prog-ress,preventive strategies remain unmet medical needs.Green tea catechins have been shown to be effective in improving aging-related cardiovascular and cerebral disorders in animal models and patients.However,little attention has been paid to whether long-term administration of epigallocatechin gallate(EGCG),the major bioactive ingredient of green tea catechins,could prevent the onset and progression of CDD.In this study,12-month-old female mice were orally administered 50,100 and 200 mg EGCG mixed with drinking water for 6 months.Aged mice(18 months old)exhibited the major features of HFpEF,including CDD with pEF,cardiac fibrosis,increased cardiomyocyte apoptosis,and mitochondrial damages,as well as elevated A/B-type natriuretic peptide.Cardiac troponin I(cTnI)expression was also reduced.Long-term administration of 100 or 200 mg EGCG prevented aging-related CDD and exercise capacity decline,along with alleviating myocardial apoptosis and mitochondria damage.The transcrip-tion and protein expression of cTnI were increased,which might be achieved by inhibiting the expression and activity of histone deacetylase 1(HDAC1),and reducing its binding level near cTnI's promoter,thereby elevating acetylated histone 3(AcH3)and acetylated lysine 9 on his-tone H3(AcH3K9)in the aged mice.We provide a novel insight that long-term administration of EGCG is a potentially effective strategy in preventing aging-related CDD and cTnI expression decline.展开更多
基金supported by grants from the Science and Technology Foundation of Chongqing,China (No.cstc2021jcyj-bshX0056)the Key Grant from the National Clinical Research Center for Child Health and Disorders (China) (No.NCRCCHD-2021-KP-01)+1 种基金the National Natural Science Foundation of China (No.81974030)the National Key Clinical Specialty (China).
文摘Aging is an independent risk factor for cardiovascular diseases.Cardiac diastolic dysfunction(CDD),ultimately leading to heart failure with preserved ejection fraction(HFpEF),is prevalent among older individuals.Although therapeutics have made great prog-ress,preventive strategies remain unmet medical needs.Green tea catechins have been shown to be effective in improving aging-related cardiovascular and cerebral disorders in animal models and patients.However,little attention has been paid to whether long-term administration of epigallocatechin gallate(EGCG),the major bioactive ingredient of green tea catechins,could prevent the onset and progression of CDD.In this study,12-month-old female mice were orally administered 50,100 and 200 mg EGCG mixed with drinking water for 6 months.Aged mice(18 months old)exhibited the major features of HFpEF,including CDD with pEF,cardiac fibrosis,increased cardiomyocyte apoptosis,and mitochondrial damages,as well as elevated A/B-type natriuretic peptide.Cardiac troponin I(cTnI)expression was also reduced.Long-term administration of 100 or 200 mg EGCG prevented aging-related CDD and exercise capacity decline,along with alleviating myocardial apoptosis and mitochondria damage.The transcrip-tion and protein expression of cTnI were increased,which might be achieved by inhibiting the expression and activity of histone deacetylase 1(HDAC1),and reducing its binding level near cTnI's promoter,thereby elevating acetylated histone 3(AcH3)and acetylated lysine 9 on his-tone H3(AcH3K9)in the aged mice.We provide a novel insight that long-term administration of EGCG is a potentially effective strategy in preventing aging-related CDD and cTnI expression decline.
