Effects Of Cardiac Resynchronization Therapy On Circadian Genes Expression In Peripheral Blood Mononuclear Cells In Patients With Chronic Heart Disease

Background:Cardiac resynchronization therapy(CRT)is an important therapy for chronic heart failure(CHF).CRT improves the sympathetic-vagal nerve activity while reversing myocardial remodeling.Our previous study confirmed that CRT can improve the heart rate variability(HRV)in patients with chronic heart failure and restore circadian clock gene expression in peripheral blood cells.Therefore,there is a relationship among CRT response,clock genes expression and autonomic nervous activity.Objective:To explore the relationship between CRT and circadian clock genes expression in peripheral blood mononuclear cells(PBMC)and screen the sensitive and specific biomarker in CRT responders.Methods:1.Echocardiography was performed in healthy volunteers and CHF patients before CRT implantation.Venous blood samples were collected at four time points of 06:00,11:00,18:00 and 23:00.Then PCR was performed to explore the influence of chronic heart failure on the expression of clock genes in PBMC.2.Six months after CRT implantation,the patients were admitted to hospital for evaluating cardiac function.According to New York Heart Function Assessment(NYHA)and echocardiography parameters,CHF patients were divided into three groups: CRT super-responders,CRT responders and CRT non-responders.Venous blood samples were also collected at four time points of 06:00,11:00,18:00 and 23:00.And PCR was performed to analysis the correction between CRT response and clock genes expression in PBMC.Results:1.The study included 23 CHF patients before CRT implantation and 10 healthy volunteers.PCR showed that clock gene expression of PER1,PER2 and PER3(PER1/2/3)in healthy people PBMC in a circadian manner with the peak level at 6:00(PER1?PER3),23:00(PER2)and trough at 11:00~18:00(PER1/2/3)while circadian rhythm of PER1/2/3 genes in CHF patients disappeared.2.According to cardiac function and echocardiography parameters,CHF patients were divided into three groups: CRT super-responders(8 patients),CRT responders(8 patients)and CRT non-responders(7 patients).In CRT super-responders and responders,CRT can restore circadian rhythm of PER1/2/3 genes.Notably,the rhythm expression of PER1 gene is significantly related to the prognosis of CHF patients.The higher the amplitude of PER1 expression,the better left ventricular ejection fraction(LVEF).Conclusions:1.The circadian rhythm expression of PER1,PER 2 and PER 3 in CHF patients PBMC disappeared.2.CRT can restore circadian rhythm of clock genes in CHF patients' PBMC,and rhythm expression of PER1 may be a reliable indicator of cardiac function improvement in CRT super-responders.