Mechanisms of adaptation of the hepatic vasculature to the deteriorating conditions of blood circulation in liver cirrhosis

Abstract

PubMed, EMBASE, Orphanet, MIDLINE, Google Scholar and Cochrane Library were searched for articles published between 1983 and 2015. Relevant articles were selected by using the following terms: "Liver cirrhosis", "Endothelial dysfunction", "Sinusoidal remodeling", "Intrahepatic angiogenesis" and "Pathogenesis of portal hypertension". Then the reference lists of identified articles were searched for other relevant publications as well. Besides gross hepatic structural disorders related to diffuse fibrosis and formation of regenerative nodules, the complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis also play important roles in hemodynamic disturbances in liver cirrhosis. It is characterized by endothelial dysfunction and impaired paracrine interaction between activated stellate hepatocytes and sinusoidal endotheliocytes, sinusoidal remodeling and capillarization, as well as development of the collateral microcirculation. In spite of the fact that complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis in liver cirrhosis are the compensatory-adaptive reaction to the deteriorating conditions of blood circulation, they contribute to progression of disease and development of serious complications, in particular, related to portal hypertension.

Surgical Portosystemic Shunts: History, Evolution, and Current Applications

“…These pathophysiological disturbances may be the initial step in the development of portosystemic collateral circulation. 9,10 Detection and Classification of Portal Hypertension PH can be classified into three main categories based on the anatomic location of flow obstruction: prehepatic, intrahepatic, and posthepatic. Intrahepatic PH can be further subdivided into presinusoidal, sinusoidal, and postsinusoidal.…”

Angiogenesis Inhibitors for the Treatment of Hepatocellular Carcinoma

“…The beginning of angiogenesis affects the equlibrium between pro-angiogenic and antiangiogenic molecules in the local tissue microenvironment (Bruix et al, 2014a; Garbuzenko et al, 2016; Kubo et al, 2016). These molecules mediate multiple steps in the process of angiogenesis by selectively altering the characteristics of endothelial cells and associated perivascular structures (i.e., pericytes, vascular smooth muscle cells).…”

“…These molecules mediate multiple steps in the process of angiogenesis by selectively altering the characteristics of endothelial cells and associated perivascular structures (i.e., pericytes, vascular smooth muscle cells). Angiogenesis can occur by either emergent or non-emergent processes (Garbuzenko et al, 2016). Emergent angiogenesis implicates the division of new small vessels from pre-existing vessels.…”

“…Non-emergent angiogenesis results from the enlargement, splitting, and fusion of pre-existing vessels produced by the proliferation of endothelial cells within the wall of a vessel. Trans-vascular bridges are occasionally observed in enlarged vessels produced by non-sprouting angiogenesis (Garbuzenko et al, 2016). This type of angiogenesis can occur concurrently with sprouting angiogenesis in the vascularization of organs or tissues.…”

Restructuring of the vascular bed in response to hemodynamic disturbances in portal hypertension

“…In addition, sinusoidal endothelial dysfunction in liver cirrhosis disturbs the balance between vasoconstrictors and vasodilators produced by the endothelium. There are endothelin-1 (ET-1) and nitrogen oxide (NO), the most studied at present[2]. …”