Remodeling of Calcium Handling in Human Heart Failure

Abstract

Heart failure (HF) is an increasing public health problem accelerated by a rapidly aging global population. Despite considerable progress in managing the disease, the development of new therapies for effective treatment of HF remains a challenge. To identify targets for early diagnosis and therapeutic intervention, it is essential to understand the molecular and cellular basis of calcium handling and the signaling pathways governing the functional remodeling associated with HF in humans. Calcium (Ca2+) cycling is an essential mediator of cardiac contractile function, and remodeling of calcium handling is thought to be one of the major factors contributing to the mechanical and electrical dysfunction observed in HF. Active research in this field aims to bridge the gap between basic research and effective clinical treatments of HF. This chapter reviews the most relevant studies of calcium remodeling in failing human hearts and discusses their connections to current and emerging clinical therapies for HF patients.

Functional State of Myocardium After Application of a Non-Cellular Allogenic Material for Stimulation of Regeneration Capacity in Experimental Infarction

“…Продолжающаяся невосполнимая гибель кардиомиоцитов в этой зоне создает условия для развития аневризмы и кардиосклероза. Именно поэ-тому правомерно говорить о развитии ремоделирова-ния на клеточном уровне, которое затрагивает и про-цесс электромеханического сопряжения в кардиомио-цитах [9,10]. Стенозирование коронарной артерии является хорошо известным способом моделирова-ния инфаркта миокарда и постинфарктного кардио-склероза в эксперименте [11].…”

“…Этот результат согласуется с ранее опубликованными нашими данными об изменении ритмоинотропной зависимости как миокарда животных с эксперимен-тальной моделью ПИКС, так и изолированных трабе-кул, выделенных из биоптатов сердца больных хро-нической ишемической болезнью сердца [12]. Анало-гичные данные сообщают и другие исследователи [9,10]. Отсутствие потенциации инотропного ответа после периодов покоя или отрицательная динамика зависимости инотропной реакции от длительности периодов покоя обусловлены изменением в работе систем, ответственных за поддержание внутрикле-точного гомеостаза ионов кальция [7,10].…”

Combination Therapy With Beta Blocker and Inotrope in Decompensated Heart Failure: A Clinical Observation

“…21 Moreover, these changes may result in improvements in inotropy and lusitropy without increasing arrhythmogenesis and cardiotoxicity. [22][23][24][25] Acute BB therapy inhibits Ca 2+ leakage from failing RyR2 even at a low dose, and addition to milrinone suppresses milrinone-induced Ca 2+ leakage from failing RyR2 , leading to greater improvement in cardiomyocyte function in dogs. 26 In the presence of BB, the harmful sustained β-receptor pathway signaling associated with HF, mediated through cAMP-independent G-α-stimulating protein coupling of calcium channels, 27 is eliminated as well.…”

Deep RNA sequencing elucidates microRNA-regulated molecular pathways in ischemic cardiomyopathy and nonischemic cardiomyopathy

“…Several of these pathways have been associated with heart disease, such as the calcium signaling and cell cycle signaling. It has been well recognized that abnormal Ca 2+ handling is a key pathophysiological mechanism in human heart failure (Lou et al, 2012). However, our understanding of the molecular and cellular mechanisms underlying altered calcium handling in the failing human heart remains incomplete.…”