Loss Of Small Vessels Research Articles

Three Dimensional Model-Based Analysis of the Lenticulostriate Arteries and Identification of the Vessels Correlated to the Infarct Area: Preliminary Results

Small vessel diseases have been studied noninvasively with magnetic resonance imaging. Direct observation or visualization of the connected microvessel to the infarct, however, was not possible due to the limited resolution. Hence, one could not determine whether vessel occlusion or abnormal narrowing is the cause of an infarct. In this report, we demonstrate that the small vessel related to the infarct can be detected using ultra-high-field (7 T) magnetic resonance imaging and a three dimensional image analysis and modeling technique for microvessels, which thereby enables us to quantify the vessel morphology directly, that is, visualize the vessel that is related to the infarct. We compared vessels of selected stroke patients, who had recovered from stroke, with vessels from typical stroke patients, who had after effects like motor weakness, and age-matched healthy subjects to demonstrate the potential of the technique. The experimental results show that typical stroke patients had overall degradation or loss of small vessels, compared with the selected patients as well as healthy subjects. The selected patients, however, had only minimal loss of vessels, except for one vessel located close to the infarct area. These preliminary results demonstrated that 7 T magnetic resonance imaging together with a three dimensional image analysis and modeling technique could provide information for detection of the vessel related to the infarct. In addition, three dimensional image analysis and modeling of vessels could further provide quantitative information on the microvessel structures comprising diameter, length and tortuosity.

Bone morphogenetic protein 2 induces pulmonary angiogenesis via Wnt–β-catenin and Wnt–RhoA–Rac1 pathways

Mutations in bone morphogenetic protein (BMP) receptor II (BMPRII) are associated with pulmonary artery endothelial cell (PAEC) apoptosis and the loss of small vessels seen in idiopathic pulmonary arterial hypertension. Given the low penetrance of BMPRII mutations, abnormalities in other converging signaling pathways may be necessary for disease development. We hypothesized that BMPRII supports normal PAEC function by recruiting Wingless (Wnt) signaling pathways to promote proliferation, survival, and motility. In this study, we report that BMP-2, via BMPRII-mediated inhibition of GSK3-β, induces β-catenin (β-C) accumulation and transcriptional activity necessary for PAEC survival and proliferation. At the same time, BMP-2 mediates phosphorylated Smad1 (pSmad1) or, with loss of BMPRII, pSmad3-dependent recruitment of Disheveled (Dvl) to promote RhoA–Rac1 signaling necessary for motility. Finally, using an angiogenesis assay in severe combined immunodeficient mice, we demonstrate that both β-C– and Dvl-mediated RhoA–Rac1 activation are necessary for vascular growth in vivo. These findings suggest that the recruitment of both canonical and noncanonical Wnt pathways is required in BMP-2–mediated angiogenesis.

Capillaries, endothelial phenotype and inflammatory markers in the Skin of Systemic Sclerosis patients, does autologous stem cell transplant induce capillary regeneration?

Systemic Sclerosis(SSc), or scleroderma, is a fibrotic, autoimmune, connective tissue disease with capillary rarefaction, intimal hyperplasia and cold induced vasospasm. Theories of pathogenesis for SSc include endothelial cell death resulting in loss of small vessels. Nail bed microscopy has suggested that loss of capillaries may be an early event in this sequence but detailed studies of capillary rarefaction have not been done. We compared endothelium from skin biopsies from 26 SSc patients, 24 normal controls, and 7 SSc patients who underwent autologous stem cell transplant (A-SCT). Our results showed an unusual endothelial phenotype in the residual vessels and decreased capillary counts in SSc. We found vascular endothelial cadherin and interferon alpha expression changes associated with SSc. Although all patients experienced clinical improvement after treatment, 5 of 7 SSc patients who received A-SCT have increased capillary counts and the above two markers have returned to normal as other clinical signs in the skin regress. These results have implications for treatment and research directions for SSc.

Chronic hypoxia causes angiogenesis in addition to remodelling in the adult rat pulmonary circulation

Chronic hypoxia caused by migration of native sea-level dwellers to high altitude or chronic lung disease leads to the development of increased pulmonary vascular resistance and pulmonary hypertension. This altitude-induced hypertension offers no obvious benefit and may indeed be maladaptive. A major mechanism thought to contribute to the development of pulmonary hypertension is hypoxia-induced loss of small blood vessels, sometimes termed rarefaction or pruning. More recent evidence caused us to question this widely accepted concept including the potent angiogenic effect of chronic hypoxia in all other vascular beds and the demonstration that new vessels can form in the pulmonary circulation when stimulated by chronic infection and lung resection. We tested the hypothesis that chronic environmental hypoxia causes angiogenesis in the adult pulmonary circulation by using stereological techniques combined with confocal microscopy to examine the resultant changes in pulmonary vascular structure in rats. We found that chronic hypoxia resulted in increased total pulmonary vessel length, volume, endothelial surface area and number of endothelial cells in vivo. This is the first reported demonstration of hypoxia-induced angiogenesis in the mature pulmonary circulation, a structural adaptation that may have important beneficial consequences for gas exchange. These findings imply that we must revise the widely accepted paradigm that hypoxia-induced loss of small vessels is a key structural change contributing to the development of pulmonary hypertension in high altitude adaptation and chronic lung disease.

Chronic hypoxia causes angiogenesis in addition to remodelling in the adult rat pulmonary circulation.

Chronic hypoxia caused by migration of native sea-level dwellers to high altitude or chronic lung disease leads to the development of increased pulmonary vascular resistance and pulmonary hypertension. This altitude-induced hypertension offers no obvious benefit and may indeed be maladaptive. A major mechanism thought to contribute to the development of pulmonary hypertension is hypoxia-induced loss of small blood vessels, sometimes termed rarefaction or pruning. More recent evidence caused us to question this widely accepted concept including the potent angiogenic effect of chronic hypoxia in all other vascular beds and the demonstration that new vessels can form in the pulmonary circulation when stimulated by chronic infection and lung resection. We tested the hypothesis that chronic environmental hypoxia causes angiogenesis in the adult pulmonary circulation by using stereological techniques combined with confocal microscopy to examine the resultant changes in pulmonary vascular structure in rats. We found that chronic hypoxia resulted in increased total pulmonary vessel length, volume, endothelial surface area and number of endothelial cells in vivo. This is the first reported demonstration of hypoxia-induced angiogenesis in the mature pulmonary circulation, a structural adaptation that may have important beneficial consequences for gas exchange. These findings imply that we must revise the widely accepted paradigm that hypoxia-induced loss of small vessels is a key structural change contributing to the development of pulmonary hypertension in high altitude adaptation and chronic lung disease.