Disturbed Diurnal Rhythm Alters Gene Expression and Exacerbates Cardiovascular Disease With Rescue by Resynchronization
| Autor: | Neelam Khaper, Fayez Dawood, Marty Straume, Denise D. Belsham, Horia Pribiag, Peter P. Liu, Michael J. Sole, Martin R. Ralph, Jennifer A. Chalmers, Nazneen Tata, Peter H. Backx, Paul Lee, Tami A. Martino |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Heart disease Gene Expression Cardiomegaly Biology Severity of Illness Index Muscle hypertrophy Mice Biological Clocks Internal medicine Internal Medicine medicine Animals Circadian rhythm Pressure overload Ventricular Remodeling Suprachiasmatic nucleus Gene Expression Profiling Myocardium Brain Microarray Analysis medicine.disease Myocardial Contraction Circadian Rhythm Cardiovascular physiology Mice Inbred C57BL ARNTL PER2 Endocrinology Echocardiography Hypertension |
| Zdroj: | Hypertension. 49:1104-1113 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | Day/night rhythms are recognized as important to normal cardiovascular physiology and timing of adverse cardiovascular events; however, their significance in disease has not been determined. We demonstrate that day/night rhythms play a critical role in compensatory remodeling of cardiovascular tissue, and disruption exacerbates disease pathophysiology. We use a murine model of pressure overload cardiac hypertrophy (transverse aortic constriction) in a rhythm-disruptive 20-hour versus 24-hour environment. Echocardiography reveals increased left ventricular end-systolic and -diastolic dimensions and reduced contractility in rhythm-disturbed transverse aortic constriction animals. Furthermore, cardiomyocytes and vascular smooth muscle cells exhibit reduced hypertrophy, despite increased pressure load. Microarray and real-time PCR demonstrate altered gene cycling in transverse aortic constriction myocardium and hypothalamic suprachiasmatic nucleus. With rhythm disturbance, there is a consequent altered cellular clock mechanism ( per2 and bmal ), whereas key genes in hypertrophic pathways ( ANF, BNP, ACE , and collagen ) are downregulated paradoxical to the increased pressure. Phenotypic rescue, including reversal/attenuation of abnormal pathology and genes, only occurs when the external rhythm is allowed to correspond with the animals’ innate 24-hour internal rhythm. Our study establishes the importance of diurnal rhythm as a vital determinant in heart disease. Disrupted rhythms contribute to progression of organ dysfunction; restoration of normal diurnal schedules appears to be important for effective treatment of disease. |
| Databáze: | OpenAIRE |
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