Altered melusin pathways involved in cardiac remodeling following acute myocardial infarction |
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| Authors: | Rong Gu Di Zheng Jian Bai Jun Xie Qing Dai Biao Xu |
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| Institution: | 1. Kaiser Permanente-Colorado, Denver, Colorado, USA;2. Denver Health Hospital and Authority, Denver, Colorado, USA;3. University of Colorado Skaggs School of Pharmacy, Denver, Colorado, USA;4. Regis University Rueckert-Hartman College for Health Professions, School of Pharmacy, Denver, Colorado, USA;1. University of Virginia, Department of Neurological Surgery, University of Virginia Health System, P.O. Box 800212, Charlottesville, VA 22908, USA;2. University of Virginia, Department of Radiology, Charlottesville, VA, USA;1. Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167 BeiLiShi Road, Beijing 100037, China;2. Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China;3. The 2nd Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China;1. Department of Clinical Toxicology, Medical University of Gdansk, Gdansk, Poland;2. Pomeranian Centre of Toxicology, Gdansk, Poland;1. From the Department of Intensive Care, Leiden University Medical Centre, Leiden, The Netherlands;2. Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands;3. Department of Thoracic Surgery, Hennigsdorf, Germany;4. Thermo Fisher Scientific/BRAHMS GmbH, Hennigsdorf, Germany;5. Leiden University Medical Centre, Leiden, The Netherlands |
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| Abstract: | BackgroundMelusin, a muscle-specific integrin-linked protein, has been reported to be a biomechanical sensor and to protect the heart from pressure overload. In the present study, we investigated the possible role that melusin plays during cardiac remodeling after myocardial infarction (MI).MethodsWe constructed a heart failure model of rats induced by left anterior descending coronary artery ligation. At different time points (1, 2, 3, 4, 6, and 8 weeks) following the operation, cardiac function was monitored by echocardiography and hemodynamic assessment; cardiac morphology was measured using hematoxylin–eosin-stained sections. Melusin expression, as well as p-Akt, Akt, and one of the Rho small GTPase family members, CDC42, was determined dynamically by Western blotting analysis during the postinfarction cardiac remodeling.ResultsProgressive increase in left ventricular (LV) end-systolic dimension and LV end-diastolic dimension and decrease in percent LV fractional shortening (%FS) and LVdp/dtmax demonstrated gradually deteriorated cardiac function in rats following MI operation. Morphological analysis revealed cardiac remodeling in MI animals, including increased LV diameter and decreased border zone thickness. We also showed a dynamic change in melusin during heart failure progression; it had an initial decline which was evident at 3 weeks and increased subsequently, reaching peak levels at 6 weeks. This dynamic change in melusin was significantly correlated with %FS and LVdp/dtmax. p-Akt/Akt and CDC42 protein expression was correlated with melusin content.ConclusionsThe altered melusin pathways and CDC42 parallel the cardiac function progression during cardiac remodeling post-MI. The dynamic change of them during this procedure may represent an important molecular mechanism underlying postinfarction cardiac remodeling and provide potential therapeutic targets. |
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