Large and micro coronary vascular involvement in diabetes. (1/1245)

Diabetes, with hyperglycemia as its hallmark, is a major risk factor for ischemic heart disease. The role of coronary disease in the adverse prognosis of diabetes is controversial although the higher prevalence and extension of coronary atherosclerosis is well recognized. The paper reviews the available evidence of coronary involvement in diabetes with particular emphases on microcirculation. Several studies, mainly in type 2 diabetes, have documented a reduced coronary flow reserve even in absence of coronary obstructive disease and using different techniques. Microcirculatory dysfunction affects the left ventricle globally as well as regionally. However, neither the prevalence of such abnormality in the diabetic population nor its time course and its prognostic value have been investigated in specifically addressed studies. In fact, a relatively large number of studies on myocardial perfusion performed by single-photon myocardial scintigraphy in asymptomatic diabetics rather address the problem of the prevalence of silent ischemia and its prognostic value. In spite of such limitation it can be speculated from the few available studies with known coronary anatomy that the prevalence of exclusively regional disturbances of perfusion (scintigraphic defects) in absence of obstructive coronary disease is not marginal as it ranges from 11 to 63%. Extensive research is still required to define the pathogenesis and the actual clinical relevance of coronary microcirculatory dysfunction in diabetes.  (+info)

Purinoceptors in renal microvessels: adenosine-activated and cytochrome P450 monooxygenase-derived arachidonate metabolites. (2/1245)

Cytochrome P450 (CYP)-dependent epoxyeicosatrienoic acids (EETs) dilate rat preglomerular microvessels (PGMVs) when adenosine 2A receptors (A(2A)R) are stimulated. As high salt intake increases epoxygenase activity and adenosine levels, we hypothesized that renal adenosine responses would be greater in high salt-fed rats. We have obtained evidence supporting this hypothesis in rats fed a high salt diet for 7 days. Stimulation of adenosine receptors with 2-chloroadenosine in kidneys obtained from rats on high salt (4%) intake produced an increase in EET release that was several-fold greater than in kidneys of rats on normal salt (0.4% NaCl) diets, which was associated with a sharp decline in renovascular resistance. Under conditions of high salt intake, an associated upregulation of A(2A)R and 2C23 protein expression was observed. As EETs are renal vasodilator and natriuretic eicosanoids, the antipressor response to salt loading may operate through an A(2A)R - EET mechanism. These findings expand the role of adenosine-related mechanisms in protecting renal function.  (+info)

Inflammatory pathways and microvascular responses in the lung. (3/1245)

Neutrophil granulocytes constitute an important host defense mechanism, but may at the same time damage functional tissue and propagate acute organ failure. This balance is particularly vulnerable in the lung which provides a large surface area for invading pathogens and microorganisms, and simultaneously harbors a large pool of physiologically marginated neutrophils within its microvascular bed. Pathophysiological stimuli further amplify this accumulation of blood cells and promote the emigration of neutrophils into the pulmonary interstitium and the airspaces by different mechanisms depending on the pathophysiological stimulus, its route of entry into or site of production in the lung, and the time course of its action. Importantly, the pulmonary microvascular endothelium plays a key role in regulating not only sequestration and emigration of neutrophils, but by initiating the inflammatory response to a variety of diverse stimuli many of which do not directly target the circulating neutrophil, but elicit microvascular reactions by primarily acting on the endothelium. This review highlights the inflammatory process in the pulmonary microvasculature with special emphasis on the role of the pulmonary endothelium.  (+info)

Effects of basic fibroblast growth factor on the expressions of angiogenic gene profile and cyclooxygenase-2 in brain microvascular endothelial cells. (4/1245)

The present study aimed to investigate the effects of basic fibroblast growth factor (bFGF) on the expressions of angioge-nesis-related genes in a mouse brain microvascular endothelial cell line, namely bEnd.3, using cDNA microarray. The effects of bFGF (10 ng/ml) on mRNA and protein expressions of cyclooxygenase-2 (COX-2), an angiogenesis bystander molecule, were further investigated. cDNA microarray was employed to study the effects of bFGF on the expressions of angiogenic genes in a high throughput pattern. RT-PCR was used to study the effect of bFGF on COX-2 mRNA expression. Western blot and immunocytochemistry were utilized to study the effect of bFGF on COX-2 protein expression. The results showed that, 2 h after bFGF treatment, pro-angiogenic genes (Adamts1, MMP-9, Ang-1, PDGF B, G-CSF, FGF16, IGF-1, etc.) were significantly upregulated, whereas anti-angiogenic genes (TIMP-2, TSP-3, etc.) were significantly downregulated. The bystander molecule in angiogenic pathway COX-2 mRNA and protein expressions were significantly upregulated after bFGF treatment. It is suggested that triggering angiogensis switch through upregulating pro-angiogenic gene and downregulating anti-angiogenic gene expression is one of the major mechanisms of bFGF-induced angiogenesis. The expression change of COX-2, as a bystander molecule, was observed after bFGF treatment in bEnd.3 cells and the significance was discussed.  (+info)

Microvascular engineering in perfusion culture: immunohistochemistry and CLSM findings. (5/1245)

BACKGROUND: One of the most challenging problems in tissue engineering is the establishment of vascular supply. A possible approach might be the engineering of microvasculature in vitro and the supply by engineered feeder vessels. METHODS: An in vitro model for a small-diameter vessel was developed and made from adipose tissue stromal cells and human umbilical vein endothelial cells in a tube-like gelatine scaffold. The number of "branches" emerging from the central lumen and the morphology of the central lumen of the vessel equivalent were assessed after 16 days of either pulsatile perfusion culture or culture in rotating containers by evaluation of immunohistochemically stained sections (n = 6 pairs of cultures). Intramural capillary network formation was demonstrated in five experiments with confocal laser scanning microscopy. RESULTS: Perfused specimens showed a round or oval lumen lined by a single layer of endothelial cells, whereas following rotation culture the lumen tended to collapse. Confocal laser scanning microscopy showed more extended network formation in perfused specimens as compared to specimens after rotation culture. Partially highly interconnected capillary-like networks were imaged which showed orientation around the central lumen. Perfused specimens exhibited significantly more branches emerging from the central lumen. There were, however, hardly any capillary branches crossing the whole vessel wall. CONCLUSION: Pulsatile perfusion supports the development of vascular networks with physiological appearance. Advances in reactor development, acquisition of functional data and imaging procedures are however necessary in order to attain the ultimate goal of a fully functional engineered supplying vessel.  (+info)

Gap junctions synchronize vascular tone within the microcirculation. (6/1245)

Gap junctions are formed in the cardiovascular system by connexin40 (Cx40), Cx37, Cx43, and Cx45. These low resistance channels allow the transfer of ions and small molecules between cells. The longitudinal coupling of endothelial and smooth muscle cells via gap junctions allows the spread of changes in membrane potential along the vascular wall and hence provides conduction pathways within the vessel itself. Functionally, this tight coupling is reflected by the spread of locally initiated vasomotor responses along the arteriole which are termed conducted responses. Conducted dilations are initiated by the application of endothelium-dependent stimuli which result in local hyperpolarization. This signal spreads along the wall, most likely along the endothelial cell layer, to elicit a coordinated dilation of the arteriole over a considerable distance. Likewise, the opposite signal (depolarization) spreads along the vessel giving rise to a conducted constriction. The latter response is however most likely transmitted along the smooth muscle cell layer. Thus, conducted responses reflect the synchronized behavior of the cells of the vascular wall. It is assumed that conducted responses are critical for the matching of oxygen delivery and tissue needs because they contribute to an ascending dilation which lowers resistance along the length of the arterioles and upstream vessels in a well-tuned fashion. Herein, Cx40 is of special importance because it is critically required for intact signal transduction along the endothelial cell layer. In addition, Cx40 mediates pressure feedback inhibition on renin synthesis in the kidney. Both, vascular and renal function of Cx40, may be involved in the hypertension that is observed in Cx40-deficient animals. In this review, we will summarize physiologic function of connexins in arterioles and briefly address their role in the kidney with respect to renin secretion.  (+info)

Tetracycline suppresses ATP gamma S-induced CXCL8 and CXCL1 production by the human dermal microvascular endothelial cell-1 (HMEC-1) cell line and primary human dermal microvascular endothelial cells. (7/1245)


Comparing contrast-enhanced color flow imaging and pathological measures of breast lesion vascularity. (8/1245)