Dysfunction of the Cardiovascular System During Diabetes
Grant N. Pierce, Robert E. Beamish, Naranjan S. Dhalla in Heart Dysfunction in Diabetes, 2019
Precedents do exist for microvascular complications during diabetes. Microvasculature lesions have been reported in other tissues of the body during diabetes. The manifestations of these microvascular defects throughout the body are numerous. Regional blood flow in many tissues of the rat is lower during experimental diabetes than in control conditions.109 Abnormal constriction of arterioles under rest conditions has also been observed in spontaneous and chemically induced diabetic animals.110,111 A hypercoagulable state has been described in serum from diabetic patients112,113 which would inevitably lead to vascular disturbances. The microvasculature of diabetic subjects was found to have an attenuated vasodilatory response to appropriate agonists110,111 and a virtual loss of the capacity to control blood flow by autoregulation.114 Significantly, capillary membrane integrity appears to be in a seriously compromised state as evidenced by the increase in permeability observed in studies of the microvasculature during diabetes.115,116 Microvessel density has been reported to decrease in various tissues during diabetes.110,111 Structural disruption in the microvasculature which accompanies diabetes may depend upon the type of vessel examined. Arterioles exhibit a degeneration of wall structure whereas the capillary basement membrane can thicken substantially during diabetes.117,118
Isolated, Perfused Microvessels
John H. Barker, Gary L. Anderson, Michael D. Menger in Clinically Applied Microcirculation Research, 2019
The majority of isolated microvessel studies are conducted on vessels taken from thin tissues or from those tissues from which microvessels can be easily dissected. This is one reason for the extensive number of studies that have been performed using hamster cheek pouch vessels. Another example of this would be the small penetrating cerebral arterioles studied by Dacey and Duling,7 which can rather easily be extracted from the surface of the cortex with minimal trauma. We50 devised a method to facilitate dissection of arterioles embedded deep in tissues such as the heart. Our original plan to study subendocardial arterioles was hampered by the lack of contrast between the arterioles and the surrounding subendocardial parenchymal tissue, so we formulated an ink-gelatin mixture that was liquid at room temperature and could be easily perfused into the coronary arterial system of a warm heart and would solidify when the heart was cooled to 4°C for dissection (see Reference 50 for details). This greatly enhanced the contrast between the vessel and the parenchymal tissue, and facilitated identification of small side branches. The method has also been used to dissect and isolate coronary venules.77
Imaging Angiogenesis
George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos in Handbook of Small Animal Imaging, 2018
As mentioned before, angiogenesis is generally defined as the growth of microvessel sprouts orchestrated by a range of angiogenic factors and involves endothelial cell proliferation and migration. In cancer, angiogenesis does not initiate malignancy but promotes tumor progression and growth. In contrast to cancer cells, endothelial cells are genomically stable, and therefore they were originally considered to be ideal targets for molecular imaging of angiogenesis. In addition, a potential target for imaging angiogenesis should relate to the molecular events associated with the initiation of the angiogenic process, which involves activation of various molecular markers localized to the endothelial cells. Therefore, evaluation of altered expression of integrins (αvβ3 and αvβ5), VEGF receptors, and FGF receptors led to the development of targeted imaging probes for imaging angiogenesis.
Recent advances in drug delivery systems for targeting brain tumors
Published in Drug Delivery, 2023
Yi Zhao, Ping Yue, Yao Peng, Yuanyuan Sun, Xing Chen, Ze Zhao, Bingjie Han
The tumor microenvironment includes tumor cells, tumor stem cells, blood vessels, lymphatic, immune cells, fibroblasts, and extracellular matrix, which provides a suitable environment for the growth, division, angiogenesis and metastasis of tumor cells (Petrova et al., 2018). And TME protects tumor cells mainly through the following mechanisms. The increased activity of vascular endothelial growth factor leads to the high proliferation of microvessels. Tumor cells interact with secreted cytokines or growth factors to obtain nutrients from abnormal blood vessels, which in turn induce fibroblasts and macrophages to proliferate and invade, resulting in drug resistance. The cross-linking structure of extracellular matrix formed by the fibrous collagen, proteoglycan, stromal cell protein and hyaluronic acid prevents drugs from reaching tumor cells through the microenvironment, thus resisting the drugs treatment. In addition to providing integral structure, extracellular matrix also contributes to the transport of nutrients and oxygen, thereby promoting tumor initiation and progression.
Effects of 4-phenylbutyric acid on the development of diabetic retinopathy in diabetic rats: regulation of endoplasmic reticulum stress-oxidative activation
Published in Archives of Physiology and Biochemistry, 2023
Amany Abdel-Ghaffar, Ghada G. Elhossary, Atef M. Mahmoud, Amany H. M. Elshazly, Olfat A. Hassanin, Anisa Saleh, Sahar M. Mansour, Fatma G. Metwally, Laila K. Hanafy, Sawsan H. Karam, Neveen Darweesh, Ahmed Mostafa Ata
There is good evidence that ER stress can be one of the contributing factors in the development of diabetic retinopathy with its vascular abnormalities such as pericyte loss and neovascularization. One of the early characteristic pathological features of diabetic retinopathy is the loss of pericytes from the microvessels. ER stress activates UPR in the retinal pericytes leading to their death (Ikesugi et al.2006). Concerning diabetic retinopathy pathogenesis, the role of vascular endothelial growth factor (VEGF) is well established where its expression is higher in diabetic retinas by hypoxia, ischaemia, and high-glucose. Such increase in expression is associated with the development of neovascularization and vascular permeability increase. It was suggested also that overexpression of VEGF can be caused by ATF4 activation mediated by ER stress (Roybal et al.2004). As reported, apoptosis induced by ER stress influences neurons’ death of the retina under various conditions (Oshitari et al. 2014). In addition, in animal models of diabetic retinopathy and retinal inflammation, multiple ER stress markers were significantly up-regulated such as GRP78, phospho-IRE1α, and phosphor-eIF2α (Li et al.2009).
Models for barrier understanding in health and disease in lab-on-a-chips
Published in Tissue Barriers, 2023
J. Ponmozhi, S. Dhinakaran, Dorottya Kocsis, Kristóf Iván, Franciska Erdő
The microvessels within the central nervous system play a critical role in not only transporting energy substrates and waste products but also in tightly regulating the movement of ions, molecules, and cells between the bloodstream and the brain. The blood-brain barrier (BBB) is a compact structure consisting of capillary endothelial cells surrounded by pericytes and astrocyte endfeet. This structure is responsible for protecting the brain from toxins and pathogens, and the properties of the BBB greatly influence the development of neurological disorders. However, this barrier also prevents the entry of drugs targeting the central nervous system. The microenvironment plays a significant role in BBB function, and fluid flow, along with precise composition, is critical in maintaining barrier function135.
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