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Hypothalamic Neuronal Circuits Are Modulated by Insulin and Impact Metabolism 1
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Tadeu de Oliveira Diz, Sabela Casado, Rubén Nogueiras, Sulay Tovar
Another cell type that may play a role in insulin signalling in hypothalamus are the pericytes, as they are a key component of the neurovascular unit, which includes endothelial cells, astrocytes, and neurons. The pericytes are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries and venules throughout the body. In the brain, they help to maintain homeostatic and haemostatic functions, they are also implicated in the sustain and permeability of the BBB (68). Pericytes have also been found to express INSRs and reside within the hypothalamus. Intriguingly, hypothalamic neurons show increased sensitivity to insulin and enhanced Akt phosphorylation in response to pericyte-conditioned media, an effect not seen in response to other cell-conditioned media (74).
Biological basis of angiogenesis and role of vascular endothelial growth factor-D
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
Within the embryo, pluripotent embryonic precursors differentiate into hemangioblasts which form blood islands. Cells at the periphery of blood islands differentiate into endothelial cells, while the cells in the center differentiate into hemopoietic precursors. Recently, it has been pointed out that there could be a common precursor for endothelial and smooth muscle cell precursors4. Embryonic stem cells in vitro can be induced to differentiate toward hemopoietic cells, endothelial cells or mural cells. Non-adherent cells will generate hemopoietic cells while adherent cells can be forced to differentiate into endothelial cells or smooth muscle cells if treated with different growth factors (Figure 1). Interestingly, specific substrates induce different percentages of one or another cell type, suggesting that integrin expression plays an important role in the differentiation pathways. The common precursors express markers like CD31, CD34 and the receptor Flk1/vascular endothelial growth factor receptor-2. Vasculogenesis is not restricted to the embryo. Bone marrow-derived angioblasts circulating can, following an induction program not yet understood, initiate a vasculogenesis process5.
IVIM MRI: A Window to the Pathophysiology Underlying Cerebral Small Vessel Disease
Published in Denis Le Bihan, Mami Iima, Christian Federau, Eric E. Sigmund, Intravoxel Incoherent Motion (IVIM) MRI, 2018
Jacobus F. A. Jansen, Sau May Wong, Walter H. Backes
Interestingly, the application of IVIM in acute stroke is typically aimed at detecting hypoperfusion, through f, D*, or fD* [13–15], whereas the application in the chronic phase (i.e., cSVD) [17182022] has revealed that these metrics are not necessarily indicative of the classical perfusion (i.e., CBF) but are more indicative of the microvascular integrity. Degeneration of the vessel wall composition and damage to the mural cells have been observed in cSVD using postmortem histopathological methods [24]. Both have been suggested to contribute to dysregulation of CBF, which can lead to the deterioration of the white matter [24]. The microvasculature was studied in cSVD using IVIM imaging, by measuring the more or less random movement of water molecules that flow into the microvascular network [17, 18]. In both studies, a higher IVIM perfusion volume fraction f was found for patients, which is surprising at first sight as CBF is typically decreased in cSVD [8], which was also found using IVIM in acute stroke [13]. Hence, a reduction of CBF (ischemia) may precede the formation of WMHs and suggests the presence of hypoperfusion in the NAWM. Moreover, evidence from a cSVD study employing dynamic contrast–enhanced (DCE) MRI reported that the blood plasma volume, a measure related to perfusion, was lower in cSVD [25]. Whereas results with DCE MRI are in line with hypoperfusion in cSVD, results of IVIM imaging point toward hyperperfusion. These results seem contraindicative.
The prediction value of platelet-derived growth factor for major adverse cardiovascular events in patients with acute non-ST-segment elevation myocardial infarction
Published in Annals of Medicine, 2023
Yan Liang, Jing-xian Wang, Xiao-Yuan Wu, Yan Cui, Zhong-He Zou, Wen-Qing Li, Yin Liu, Jing Gao
Based on the pivotal role of PDGF in anti-apoptosis and vasculogenic effects, PDGF may be a novel treatment target for heart failure. Activation of PDGFR signalling attenuates post-infarction remodelling and may have important therapeutic implications for survivors of acute MI [24]. In the MI animal model by Hsieh et al. [22], local delivery of PDGF significantly improved LVEF and cardiac index and significantly reduced end-diastolic volume, suggesting that PDGF attenuated remodelling in treated animals. In the study by Cui et al. [25], dual gene therapy with bFGF and PDGF showed a marked angiogenic effect, with concomitant significant reduction in infarct size and improved cardiac function. The possible mechanisms are as follows: First, PDGF-induced activation of endothelial cells may promote angiogenesis, thereby increasing capillary density in the infarct border zone [26]. Second, PDGFR-β activation in mural cells may promote vascular maturation. Third, enhanced PDGFR-α signalling may improve the repair function of fibroblasts and promote organized collagenous scar formation, which is critical for protecting the ventricle from rupture and adverse remodelling [27].
Gastrointestinal bleeding in von Willebrand patients: special diagnostic and management considerations
Published in Expert Review of Hematology, 2023
Edwin Ocran, Nicholas L.J. Chornenki, Mackenzie Bowman, Michelle Sholzberg, Paula James
The key molecules that mediate the stabilization and maturation of new vessels are Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) which bind to the tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie-2) receptor on ECs, resulting in antagonistic effects [49]. Ang-1 is synthesized by mural cells (vascular smooth muscle cells and pericytes) and stimulates the recruitment of pericytes, prompting vessel maturity and reducing vascular leakage [50]. On the other hand, Ang-2 which is produced by ECs and stored in Weibel-Palade bodies (WPBs) along with VWF (Figure 1), competitively inhibits the binding of Ang-1, thus, promoting the destabilization of the vessel by acting synergistically with VEGF [51,52]. A delicate balance between these antagonistic molecules is crucial to normal angiogenesis.
Recent developments in the pathobiology of lung myofibroblasts
Published in Expert Review of Respiratory Medicine, 2021
Dingyuan Jiang, Tapan Dey, Gang Liu
Pericytes are multi-functional mural cells that wrap around the endothelial cells of micro-vasculatures [25]. These cells have been implicated as a source of myofibroblasts in several organs, including the lung [25,26]. This concept seemed credible because pericytes are a major type of mesenchymal cells. Furthermore, the number of these cells was increased substantially in the lungs of bleomycin-treated mice [25]. Cell lineage tracing study that labeled pericytes with fluorescence under the control of the promoter of the pericyte marker neuron-glial antigen 2 (NG2) showed that these cells did not express significant α-SMA [27]. This study seems to have ruled out pericytes as an origin or lung myofibroblasts. However, NG2 might not label all pericyte population. Following study tracing Forkhead box D1 (Foxd1)+ progenies in adult lung found that they contained an extensive population of mesenchymal cells, including those expressing pericyte markers PDGFRβ and CD146, a.k.a. melanoma cell adhesion molecule (MCAM) [28]. Foxd1+ pericytes demonstrated significantly increased α-SMA expression in the lung of mice with bleomycin-induced pulmonary fibrosis. There is also evidence showing that human pericytes adopted myofibroblast properties in IPF lungs [29]. Despite these findings, scRNA-seq on Col1A1+ lung mesenchymal cells showed that although pericytes had high level of α-SMA, they only demonstrated a modest Col1A1 expression [15].