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Chronic liver disease (CLD) can be defined as a complex pathophysiological process of the liver that involves a progressive destruction and regeneration of the liver parenchyma leading to fibrosis, cirrhosis, and an increasing risk of hepatocellular carcinoma (HCC). Viral hepatitis and alcohol are considered the two most important etiologies for CLD, although nonalcoholic fatty liver disease (NAFLD) is also increasingly being recognized as a common cause. [ABSTRACT FROM AUTHOR]

Stroke and Alzheimer΄s disease (AD) are leading causes of dementia in developed countries. Up until now, both diseases, vascular dementia (VaD) and AD were considered as completely different entities with their own physiopathology. The former due to a brain circulation impairment, and the latter due to a primary brain degenerative disorder. However recent epidemiological studies as well as neuropathological findings have suggested common features between both entities. Thus some authors have suggested the `vascular hypothesis of AD΄, considering AD as a vascular disease with neurodegenerative consequences or `vasocognopathy΄. This has pharmacological implications as it opens up the possibility for novel therapeutic approaches for treatment of AD, for example by stimulation of angiogenesis in the brain. [ABSTRACT FROM AUTHOR]

Angiogenesis is a frequent hallmark of inflammation; in acute inflammation angiogenesis occurs to revascularize damaged tissues, with subsequent vascular pruning and maturation, which results in restoration of an adequate blood supply to the tissue involved. Angiogenesis is also a characteristic of chronic inflammation, and may be one of the links between inflammation and cancer (Colotta et al. 2009; Kobayashi and Lin 2009). [ABSTRACT FROM AUTHOR]

Angiogenesis is a physiological process involving the formation of new blood vessels from existing vessels. It is essential for the growth of primary tumor and local tumor invasion and metastasis. This chapter reviews the general angiogenesis process, the endogenous factors that regulate angiogenesis, and therapeutic angiogenesis inhibitors. It also reviews the effect of vitamin D on angiogenesis. Vitamin D receptor is detected on endothelial cells and vascular smooth muscle cells (VSMCs). 1,25D3 has anti-proliferative effects on tumor-derived endothelial cells through the induction of cell cycle arrest and apoptosis. Increasing evidence supports an anti-angiogenic role of 1,25D3 in a number of in vivo tumor model systems. However, vitamin D promotes angiogenesis in more physiological settings. Besides endothelial cells, vitamin D affects the physiological functions and pathology of VSMCs, including cell growth, contractility, motility, and the evolution of vascular calcification, which are involved in cardiovascular diseases. In summary, vitamin D plays important roles in vasculature and angiogenesis. Preclinical studies support the anti-angiogenic effect and the use of 1,25D3 in cancer therapy. [ABSTRACT FROM AUTHOR]

Endothelial cells regulate multiple vascular functions, such as vascular tone, permeability, remodeling, and angiogenesis. It is known for long that cytosolic Ca2+ level ([Ca2+]i) and membrane potential of endothelial cells are crucial factors to initiate the signal transduction cascades, leading to diverse vascular functions. Among the various kinds of endothelial ion channels that regulate ion homeostasis, transient receptor potential (TRP) channels emerge as the prime mediators for a diverse range of vascular signaling. The characteristics of TRP channels, including subunit heteromultimerization, diverse ion selectivity, and multiple modes of activation, permit their versatile functional roles in vasculatures. Substantial amount of evidence demonstrates that many TRP channels in endothelial cells participate in physiological and pathophysiological processes of vascular system. In this article, we summarize the recent findings of TRP research in endothelial cells, aiming at providing up-to-date information to the researchers in this rapidly growing field. [ABSTRACT FROM AUTHOR]

An important feature of tumor blood vessels is that they are in a state of constant new tumor blood vessel growth. In endothelial cells, the PI3K/Akt pathway has been shown to play an important role in mediating cell survival, proliferation, and migration. The serine/threonine kinase, mammalian target of rapamycin (mTOR), an important downstream target of PI3K/Akt and mTOR signaling, has been shown to be involved in the control of cell growth and proliferation. To grow beyond a certain size primary tumor and metastases are dependent on the formation of new blood vessels or angiogenesis. In angiogenesis mTOR serves as a central regulator. There is growing evidence in support of the hypothesis that mTOR acts as a critical switch for endothelial cellular catabolism and anabolism, thus determining whether these cells grow and proliferate. This is especially critical in cancer cells bearing disturbances in the TOR pathway. There are several human cancers whereby the PI3K/Akt pathway is dysregulated. Gain or loss mutations of this pathway lead to neoplastic transformation. mTOR inhibitors downregulate hypoxia-inducible factor 1α (HIF1α)-mediated production of pro-angiogenic cytokine, vascular endothelial growth factor (VEGF), by tumor cells and the resulting activation of vascular endothelial growth factor receptors (VEGF-Rs) on endothelial and lymphatic precursor cells inhibiting survival and growth-promoting signals that support tumor vascularization and tumorigenesis. The antiangiogenic and antilymphangiogenic effects of mTOR inhibition may well translate into a reduced incidence of clinically apparent malignancies through reduced tumor growth and lymphatic metastasis, respectively. [ABSTRACT FROM AUTHOR]

Abiotrophia defectiva, one of the oral streptococci, possessed a relatively higher adhesive ability to the cultured human umbilical vein endothelial cells (HUVEC) as well as fibronectin and vitronectin than other oral streptococci tested. Further, A. defectiva induced HUVEC to produce IL-8 and TNF-α, and subsequently to express E-selectin, ICAM-1 and VCAM-1. Thus, A. defectiva entering into blood streams could adhere to endothelial cells and induce proinflammatory responses through cytokine productions and leukocyte adhesion molecule expressions. [ABSTRACT FROM AUTHOR]