Cardiovascular research
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Cardiovascular research · May 2011
The serotonin transporter, gender, and 17β oestradiol in the development of pulmonary arterial hypertension.
Idiopathic and familial forms of pulmonary arterial hypertension (PAH) predominantly affect females through an unknown mechanism. Activity of the serotonin transporter (SERT) may modulate the development of PAH, and mice overexpressing SERT (SERT+ mice) develop PAH and severe hypoxia-induced PAH. In the central nervous system, oestrogens influence activity of the serotonin system. Therefore, we examined the influence of gender on the development of PAH in SERT+ mice and how this is modulated by female hormones. ⋯ 17β oestradiol is critical to the development of PAH and severe hypoxia-induced PAH in female SERT+ mice. In hPASMCs, 17β oestradiol-induced proliferation is dependant on de novo serotonin synthesis and stimulation of the 5-HT(1B) receptor. These interactions between the serotonin system and 17β oestradiol may contribute to the increased risk of PAH associated with female gender.
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Cardiovascular research · Apr 2011
ReviewIschaemic heart disease in women: are there sex differences in pathophysiology and risk factors? Position paper from the working group on coronary pathophysiology and microcirculation of the European Society of Cardiology.
Cardiovascular disease (CVD) is the leading cause of death in women, and knowledge of the clinical consequences of atherosclerosis and CVD in women has grown tremendously over the past 20 years. Research efforts have increased and many reports on various aspects of ischaemic heart disease (IHD) in women have been published highlighting sex differences in pathophysiology, presentation, and treatment of IHD. Data, however, remain limited. ⋯ Coronary endothelial dysfunction and microvascular disease have been proposed as important determinants in the aetiology and prognosis of IHD in women, but research is limited on whether sex differences in these mechanisms truly exist. Differences in the epidemiology of IHD between women and men remain largely unexplained, as we are still unable to explain why women are protected towards IHD until older age compared with men. Eventually, a better understanding of these processes and mechanisms may improve the prevention and the clinical management of IHD in women.
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Cardiovascular research · Apr 2011
Arterial injury promotes medial chondrogenesis in Sm22 knockout mice.
Expression of SM22 (also known as SM22alpha and transgelin), a vascular smooth muscle cells (VSMCs) marker, is down-regulated in arterial diseases involving medial osteochondrogenesis. We investigated the effect of SM22 deficiency in a mouse artery injury model to determine the role of SM22 in arterial chondrogenesis. ⋯ These findings suggest that disruption of SM22 alters the actin cytoskeleton and promotes chondrogenic conversion of VSMCs.
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Cardiovascular research · Feb 2011
Soluble FLT1 sensitizes endothelial cells to inflammatory cytokines by antagonizing VEGF receptor-mediated signalling.
Pre-eclampsia affects 5-7% of pregnancies, and is a major cause of maternal and foetal death. Elevated serum levels of placentally derived splice variants of the vascular endothelial growth factor (VEGF) receptor, soluble fms-like tyrosine kinase-1 (sFLT1), are strongly implicated in the pathogenesis but, as yet, no underlying mechanism has been described. An excessive inflammatory-like response is thought to contribute to the maternal endothelial cell dysfunction that characterizes pre-eclampsia. We hypothesized that sFLT1 antagonizes autocrine VEGF-A signalling, rendering endothelial cells more sensitive to pro-inflammatory factors also released by the placenta. We tested this by manipulating VEGF receptor signalling and treating endothelial cells with low doses of tumour necrosis factor-α (TNF-α). ⋯ Our data describe a mechanism by which sFLT1 sensitizes endothelial cells to pro-inflammatory factors, providing an explanation for how placental stress may precipitate the pre-eclamptic syndrome.
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Cardiovascular research · Feb 2011
Role of the autonomic nervous system in cardioprotection by remote preconditioning in isoflurane-anaesthetized dogs.
Remote ischaemic preconditioning (rIPC) protects cardiac and non-cardiac tissues against ischaemic injury. Although there is increased demand to investigate its potential clinical applicability, fundamental mechanisms responsible for rIPC-mediated protection remain unresolved. We examined in isoflurane-anaesthetized dogs whether an intact cardiac nervous system was necessary to mediate rIPC protection against ischaemic injury. ⋯ We report robust myocardial protection by rIPC against ischaemic injury in canines that was not abrogated by either pharmacological or surgical decentralization of cardiac nerves.