The mechanisms of the evolution and development of the heart in metazoans are highlighted, starting with the evolutionary origin of the contractile cell, supposedly the precursor of cardiomyocytes.... Show moreThe mechanisms of the evolution and development of the heart in metazoans are highlighted, starting with the evolutionary origin of the contractile cell, supposedly the precursor of cardiomyocytes. The last eukaryotic common ancestor is likely a combination of several cellular organisms containing their specific metabolic pathways and genetic signaling networks. During evolution, these tool kits diversified. Shared parts of these conserved tool kits act in the development and functioning of pumping hearts and open or closed circulations in such diverse species as arthropods, mollusks, and chordates. The genetic tool kits became more complex by gene duplications, addition of epigenetic modifications, influence of environmental factors, incorporation of viral genomes, cardiac changes necessitated by air‐breathing, and many others. We evaluate mechanisms involved in mollusks in the formation of three separate hearts and in arthropods in the formation of a tubular heart. A tubular heart is also present in embryonic stages of chordates, providing the septated four‐chambered heart, in birds and mammals passing through stages with first and second heart fields. The four‐chambered heart permits the formation of high‐pressure systemic and low‐pressure pulmonary circulation in birds and mammals, allowing for high metabolic rates and maintenance of body temperature. Crocodiles also have a (nearly) separated circulation, but their resting temperature conforms with the environment. We argue that endothermic ancestors lost the capacity to elevate their body temperature during evolution, resulting in ectothermic modern crocodilians. Finally, a clinically relevant paragraph reviews the occurrence of congenital cardiac malformations in humans as derailments of signaling pathways during embryonic development. Show less
INTRODUCTION\nThe differential insertion of the atrioventricular valves is the ultrasonographic representation of the more apical attachment of the tricuspid valve to the septum with respect to the... Show moreINTRODUCTION\nThe differential insertion of the atrioventricular valves is the ultrasonographic representation of the more apical attachment of the tricuspid valve to the septum with respect to the mitral valve. A linear insertion is present when both valves form a linear continuum and is suggested as a marker for atrioventricular septal defects (AVSDs). The objective is to evaluate the anatomical substratum of differential and linear insertion of the atrioventricular valves in normal fetal hearts and fetal hearts with an AVSD.\nMETHODS\nThe extent and position of the fibrous skeleton and attachment of atrioventricular valves to the septum were studied in histological sections of 17 normal hearts and 4 hearts with an AVSD (10 + 0 weeks gestation - 3 days postpartum) with various immunohistochemical tissue markers. In addition, STIC volumes of 10 normal hearts and STIC volumes of 8 hearts with AVSD (13 + 6 - 35 + 5 weeks gestational age) were examined.\nRESULTS\nThe differential insertion of the atrioventricular valves was visible in normal hearts in the four-chamber plane immediately beneath the aorta. More towards the diaphragm, a linear insertion was found. In hearts with an AVSD, a linear appearance was observed in the four-chamber plane immediately beneath the aorta. Towards the diaphragm, however, first a differential and more caudal, a linear insertion was found.\nCONCLUSION\nBoth differential and linear insertion can be found in normal fetal hearts and fetal hearts with AVSD, dependent on the plane in which the four-chamber view is visualised. Therefore, measurement of the differential insertion is probably only useful in experienced hands. Show less
Introduction: We previously showed that human cardiomyocyte progenitor cells (hCMPCs) injected after myocardial infarction (MI) had differentiated into cardiomyocytes in vivo 3 months post MI. Here... Show moreIntroduction: We previously showed that human cardiomyocyte progenitor cells (hCMPCs) injected after myocardial infarction (MI) had differentiated into cardiomyocytes in vivo 3 months post MI. Here, we investigated the short-term (2 weeks) effects of hCMPCs on the infarcted mouse myocardium. Methods: MI was induced in immunocompromised (NOD/scid) mice, immediately followed by intramyocardial injection of hCMPCs labeled with enhanced green fluorescent protein (hCMPC group) or vehicle only (control group). Sham-operated mice served as reference. Cardiac performance was measured 2 and 14 days after MI by magnetic resonance imaging at 9.4T. Left ventricular (LV) pressure-volume measurements were performed at day 15 followed by extensive immunohistological analysis. Results: Animals injected with hCMPCs demonstrated a higher LV ejection fraction, lower LV end-systolic volume and smaller relaxation time constant than control animals 14 days post MI. hCMPCs engrafted in the infarcted myocardium, did not differentiate into cardiomyocytes, but increased vascular density and proliferation rate in the infarcted and border zone area of the hCMPC group. Conclusions: Injected hCMPCs engraft into murine infarcted myocardium where they improve LV systolic function and attenuate the ventricular remodeling process 2 weeks post MI. Since no cardiac differentiation of hCMPCs was evident after 2 weeks, the observed beneficial effects were most likely mediated by paracrine factors, targeting amongst others vascular homeostasis. These results demonstrate that hCMPCs can be applied to repair infarcted myocardium without the need to undergo differentiation into cardiomyocytes. Show less
