Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

Prandota, J

doi:10.17554/j.issn.2309-6861.2017.04.130

Cited by 1 publication

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References 611 publications

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“…Systemic sclerosis (SSc) is another autoimmune disease characterized by vascular obliteration, excessive extracellular matrix deposition, and fibrosis of the connective tissues of the skin, lung, gastrointestinal tract, heart, and kidneys. Endothelial cell dysfunction and damage represent one of the first disturbances in the pathogenesis of SSc, and chronic inflammation plays an important role in the development of atherosclerotic plaques [86] . A 60-kDa protein belonging to the heat shock proteins (HSPs) was suggested to be involved in the pathomechanism of these abnormalities [87] .…”

Section: Cryptogenic Liver Cirrhosis (Clc)mentioning

confidence: 99%

Unexplained Liver Damage, Cryptogenic Liver Cirrhosis, and Steatohepatitis May Be Caused by Latent Chronic Toxoplasmosis

Prandota

2019

Journal of Gastroenterology and Hepatology Research

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T. gondii is a globally distributed intracellular protozoan parasite affecting approximately 5-90% of human population and causing a variety of so far neglected diseases and clinical entities in both immunocompromised and immunocompetent individuals. Acute infection of the parasite in mice caused marked reduction in serum butyrylcholinesterase (BChE) activity and liver damage. BChE and acetylcholinesterase (AChE) are biomarkers of low-grade systemic inflammation and earlier it was suggested that the elevation of these two bioparameters may predict development of type 2 diabetes mellitus and Alzheimer's disease. Serum BChE activity was found to be associated with overweight, obesity, and body fat distribution parameters. Recently, a positive association between T. gondii seropositivity and obesity has also been reported. Infection with the parasite was linked with the increase in the number of hepatic stellate cells known to play an important role in the development of fibrosis and its advancement to cirrhosis.of any etiology. Moreover, several authors suggested that hepatitis with a clinical picture resembling acute viral hepatitis result from T. gondii infection. Abnormalities associated with cryptogenic liver cirrhosis markedly affect acquired immunity of the host and probably participate in triggering and persistence of several autoimmune diseases, especially that anti-T. gondii IgG antibodies have been found in the sera of both patients suffering from these clinical entities and in healthy individuals. Oxidative stress and immunosuppresion due to the infection play an important role in these processes. It should be also noted that mammalian as well as the parasite cells, express two cholesteryl ester-synthesizing enzymes, ACAT1 and ACAT2, which share 44-47% of amino acid homology. ACAT1 is present in various cells and tissues, while ACAT2 expression is restricted to hepatocytes and intestinal mucosal cells. The parasite enzymes TgACAT1 and TgACAT2 localized to endoplasmic reticulum can synthesize and store abundant esters of cholesterol and triglycerides. The lifelong persistence and resulting surplus of ACAT1 and ACAT2, and TgACAT1 and TgACAT2 enzymatic activities especially in hepatocytes and/or intestinal cells of the host may therefore at least in part be responsible for development of steatohepatitis, and generation of ballooning hepatocytes, foamy macrophages, and clear cells (foamy) colitis. These abnormalities can be explained by the suppressed autophagy (it regulates lipid metabolism) in the liver due to proliferation of T. gondii. In alcoholic steatohepatitis, ballooning degeneration of hepatocytes may also at least partly result from the fact that ethanol dose-dependently stimulate microneme secretion in T. gondii tachyzoites and parasite attachment to the host cells, thus facilitating infection of the hepatic cells. The increased serum iron levels and hepatic iron overload reported in the patients with nonalcoholic hepatitis may be caused by the excess of NO produced by activated macrophages and h...

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Section: Cryptogenic Liver Cirrhosis (Clc)mentioning

confidence: 99%