Peripartum cardiomyopathy (PPCM) is a cause of pregnancy-associated heart failure. It typically develops during the last month of, and up to 6 months after, pregnancy in women without known cardiovascular disease. The present position statement offers a state-of-the-art summary of what is known about risk factors for potential pathophysiological mechanisms, clinical presentation of, and diagnosis and management of PPCM. A high index of suspicion is required for the diagnosis, as shortness of breath and ankle swelling are common in the peripartum period. Peripartum cardiomyopathy is a distinct form of cardiomyopathy, associated with a high morbidity and mortality, but also with the possibility of full recovery. Oxidative stress and the generation of a cardiotoxic subfragment of prolactin may play key roles in the pathophysiology of PPCM. In this regard, pharmacological blockade of prolactin offers the possibility of a disease-specific therapy.--
Abstract-Heart failure remains a leading cause of morbidity and mortality. The cellular mechanism underlying the development of cardiac dysfunction is a decrease in the number of viable cardiomyocytes. Recent observations have suggested that the adult heart may contain a progenitor cell population. Side population (SP) cells, characterized by a distinct Hoechst dye efflux pattern, have been shown to exist in multiple tissues and are capable of tissue-specific differentiation. In this report, we confirm the existence of a cardiac SP cell population, immunophenotypically distinct from bone marrow SP cells. Moreover, we demonstrate that among cardiac SP cells, the greatest potential for cardiomyogenic differentiation is restricted to cells negative for CD31 expression and positive for stem cell antigen 1 (Sca1) expression (CD31 Ϫ /Sca1 ϩ ). Furthermore, we determine that CD31 Ϫ /Sca1 ϩ cardiac SP cells are capable of both biochemical and functional cardiomyogenic differentiation into mature cardiomyocytes, with expression of cardiomyocyte-specific transcription factors and contractile proteins, as well as stimulated cellular contraction and intracellular calcium transients indistinguishable from adult cardiomyocytes. We also determine the necessity of cell-extrinsic signaling through coupling, although not fusion, with adult cardiomyocytes in regulating cardiomyogenic differentiation of cardiac SP cells. We, therefore, conclude that CD31 Ϫ /Sca1 ϩ cardiac SP cells represent a distinct cardiac progenitor cell population, capable of cardiomyogenic differentiation into mature cardiomyocytes through a process mediated by cellular coupling with adult cardiomyocytes. (Circ Res. 2005;97:52-61.)
Background
The EURObservational Research Programme is a rolling programme of cardiovascular registries and surveys of the European Society of Cardiology (ESC). These registries will provide information on the nature of cardiovascular disease and its management. This manuscript provides an update on new literature on peripartum cardiomyopathy (PPCM), published since the 2010 Position Statement from the Heart Failure Association of the European Society of Cardiology Working Group on PPCM, and describes a new registry on this under‐recognized condition. Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular systolic dysfunction towards the end of the pregnancy, or in the months following delivery, where no other cause for heart failure is found.
Aims
The PPCM Registry aims to describe disease presentation, comorbidities, diagnostic and therapeutic management of patients with PPCM, as well as information on their offspring. Centres not only from ESC and ESC‐affiliated countries, but from around the world, are encouraged to participate.
Methods
A prospective registry on patients presenting with PPCM. At the time of writing, approximately 100 patients have been enrolled from 20 countries. All data entry is online via secure passwords and is supported by well‐trained information technology personnel.
Conclusion
The EURObservational Research Programme will allow a comparison of women from around the world, from different ethnic backgrounds, presenting with PPCM and will report on their 6 month and 12 month outcomes. The study aims to include 1000 patients and follow them for 1 year. New centres volunteering to participate in the study will be welcomed.
Tissue-specific progenitor cells contribute to local cellular regeneration and maintain organ function. Recently, we have determined that cardiac side-population (CSP) cells represent a distinct cardiac progenitor cell population, capable of in vitro differentiation into functional cardiomyocytes. The response of endogenous CSP to myocardial injury, however, and the cellular mechanisms that maintain this cardiac progenitor cell pool in vivo remain unknown. In this report we demonstrate that local progenitor cell proliferation maintains CSP under physiologic conditions, with little contribution from extracardiac stem cell sources. Following myocardial infarction in adult mice, however, CSP cells are acutely depleted, both within the infarct and noninfarct areas. CSP pools are subsequently reconstituted to baseline levels within 7 days after myocardial infarction, through both proliferation of resident CSP cells, as well as through homing of bone marrow-derived stem cells (BMC) to specific areas of myocardial injury and immunophenotypic conversion of BMC to adopt a CSP phenotype. We, therefore, conclude that following myocardial injury, cardiac progenitor cell populations are acutely depleted and are reconstituted to normal levels by both self-proliferation and selective homing of BMC. Understanding and enhancing such processes hold enormous potential for therapeutic myocardial regeneration.T issue-specific progenitor cell populations maintain the regenerative capacity of terminally differentiated organs, both under basal conditions and following local tissue injury. Side population (SP) cells, characterized by their intrinsic capacity to efflux Hoechst dye through ATP-binding cassette transporters, contribute to the long-term regenerative potential of hematopoietic and extrahematopoietic tissues. 1 Recently, we have demonstrated that cardiac SP (CSP) cells, immunophenotypically distinct from bone marrow (BM)-derived stem cells (BMC), are present in the adult heart and are capable of both biochemical and functional cardiomyogenic differentiation into mature cardiomyocytes, thereby identifying CSP as a distinct cardiac progenitor cell population. 2 Supplementation of cardiac progenitor cell pools after myocardial infarction (MI) with exogenous cells has been shown to improve ventricular function by regenerating myocardium and cardiac vasculature. [3][4][5] The response of endogenous CSP cells to myocardial injury, however, and the cellular mechanisms that maintain this endogenous cardiac progenitor cell pool under basal and after injury conditions remain unknown. We, therefore, serially assessed CSP pools in hearts following MI and determined the role of selfproliferation and BMC in reconstituting cardiac progenitor pools.
Methods and MaterialsCSP were isolated from mouse hearts as described previously. 2 MI was performed in mice via permanent coronary ligation. 6 BM transplantation was performed in lethally irradiated mice using marrow isolated from C57bl/6-Tg(ACTbEGFP) mice. 7 All animals were obtained from The ...
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