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OPEN ACCESS PLUS
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Contents
5(4): Pp. 289 - 295
Masaki Ieda and Keiichi Fukuda
[Open Access Plus] |
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The heart is extensively innervated and its performance is tightly controlled by the nervous system. Cardiac innervation density varies in diseased hearts leading to unbalanced neural activation and lethal arrhythmia. Diabetic sensory neuropathy causes silent myocardial ischemia, characterized by loss of pain perception during myocardial ischemia, which is a major cause of sudden cardiac death in diabetes mellitus (DM). Despite its clinical importance, the mechanisms underlying the control and regulation of cardiac innervation remain poorly understood. We found that cardiac innervation is determined by the balance between neural chemoattractants and chemorepellents within the heart. Nerve growth factor (NGF), a potent chemoattractant, is induced by endothelin-1 upregulation during development and is highly expressed in cardiomyocytes. By comparison, Sema3a, a neural chemorepellent, is highly expressed in the subendocardium of early stage embryos, and is suppressed during development. The balance of expression between NGF and Seme3a leads to epicardial-to-endocardial transmural sympathetic innervation patterning. We also found that downregulation of cardiac NGF leads to diabetic neuropathy, and that NGF supplementation rescues silent myocardial ischemia in DM. Cardiac innervation patterning is disrupted in Sema3a-deficient and Sema3aoverexpressing mice, leading to sudden death or lethal arrhythmias. The present review focuses on the regulatory mechanisms underlying cardiac innervation and the critical role of these processes in cardiac performance.
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4(4): Pp. 275 - 286
Toshio Imanishi, Hiroto Tsujioka and Takashi Akasaka
[Open Access Plus] |
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The identification of endothelial progenitor cells (EPCs) has led to a significant paradigm in the field of vascular biology and opened a door to the development of new therapeutic approaches. Based on the current evidence, it appears that EPCs may make both direct contribution to neovascularization and indirectly promote the angiogenic function of local endothelial cells via secretion of angiogenic factors. This concept of arterial wall repair mediated by bone marrow (BM)-derived EPCs provided an alternative to the local “response to injury hypothesis” for development of atherosclerotic inflammation. Increased oxidant stress has been proposed as a molecular mechanism for endothelial dysfunction, in part by reducing nitric oxide (NO) bioavailability. EPCs function may also be highly dependent on a well-controlled oxidant stress because EPCs NO bioavailability (which is highly sensitive to oxidant stress) is critical for their in vivo function. The critical question is whether oxidant damage directly leads to an impairment in EPCs function. It was revealed that activation of angiotensin II (Ang II) type 1 receptor stimulates nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase in the vascular endothelium and leads to production of reactive oxygen species. We observed that Ang II accelerates both BM- and peripheral blood (PB)-derived EPCs senescence by a gp91phox-mediated increase of oxidative stress, resulting in EPCs dysfunction. Consistently, both Ang II receptor 1 blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors have been reported to increase the number of EPCs in patients with cardiovascular disease. In this review, we describe current understanding of the contributions of oxidative stress in cardiovascular disease, focusing on the potential mechanisms of EPCs senescence.
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3(4): Pp. 232 - 239
Amy Z. Fan
[Open Access Plus] |
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The metabolic syndrome (MSynd) refers to a clustering of cardiovascular risk factors characterized by obesity, impaired glucose tolerance/type 2 diabetes, atherogenic dyslipidemia, and hypertension. The tendency that multiple risk factors were often present in the same individual prompted researchers to search for the underlying pathophysiology of the MSynd. In an inventory of hypotheses on causative mechanisms for the MSynd, plausible mechanisms include insulin resistance, leptin resistance, visceral obesity, beta-cell dysfunction, endothelial dysfunction, neuroendocrine origin (sympathetic overactivity and vagal impairment, reduced serotonergic responsivity, endocannabinoid system overactivity), genetic predisposition and fetal origin. The etiology of the syndrome is complex and each hypothesis may explain part of the etiological cascade. More studies are needed to elucidate relevance of and relationship between diverse hypotheses.
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2(3): Pp. 205 - 213
Susanne S. Pedersen and Johan Denollet
[Open Access Plus] |
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The distressed personality (Type D) is an emerging risk factor in cardiovascular disease (CVD) that incurs a risk on par with left ventricular dysfunction in patients with ischemic heart disease. Type D is defined as the co-occurring tendencies to experience increased negative emotions and to inhibit self-expression in social interactions. Evidence is accumulating that Type D may also be a risk factor for adverse outcome across CVD patient groups, including patients undergoing revascularization with drug-eluting stent implantation or bypass surgery, patients with heart failure, peripheral arterial disease, and arrhythmia. In these patient groups, Type D personality has been associated with a 2-5 fold increased risk of adverse prognosis, impaired quality of life and symptoms of anxiety and depression independent of traditional biomedical risk factors, including disease severity. Although little is known about the pathways responsible for the detrimental effects of Type D on clinical outcome, the immune system and health-related behaviors, such as smoking and noncompliance, are likely candidates. Further research is warranted to investigate whether Type D personality is here to stay as a risk factor for CVD, but weighing current evidence on Type D against a set of external criteria shows that Type D personality fulfills the majority of these criteria. Importantly, Type D can easily be assessed in clinical research and practice with the standardized and validated DS14.
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