Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Niemann-Pick C1-like 1 (NPC1L1) protein is identified as a key molecule of cholesterol absorption into the intestine. Although there is a controversy about the association between sitosterol levels and cardiovascular disease (CVD), cholesterol absorption may contribute to the increased risk for CVD because increased levels of sitosterol, a marker of cholesterol absorption, are associated with future cardiovascular events in high-risk patients. However, which anthropometric and metabolic variables could regulate serum levels of sitosterol in humans and whether serum sitosterol levels might reflect transport function of NPC1L1 are largely unknown. In this study, we first investigated the independent determinants of serum sitosterol levels in apparently healthy patients not taking lipid-lowering agents. We next examined the effects of angiotensin II on NPC1L1 gene and protein expression in differentiated Caco-2 cells. Seventy apparently health patients not taking lipid-lowering agents (28 men and 42 women, mean age 73.7+/-10.1 years old) underwent a complete history and physical examination, determination of blood chemistries, including serum levels of sitosterol. Univariate regression analysis showed that serum levels of sitosterol were associated with low-density-lipoprotein (LDL)-cholesterol (r=0.284, p=0.021) and use of the renin-angiotensin system (RAS) inhibitors (r=-0.289, p=0.018). By the use of multiple stepwise regression analyses, use of RAS inhibitors (p=0.025) was remained significant independently. Further, angiotensin II was found to up-regulate NPC1L1 mRNA and protein levels in Caco-2 cells, which were completely blocked by an angiotensin II type 1 receptor blocker or an anti-oxidant, N-acetylcysteine. The present study suggests the possible involvement of RAS in NPC1L1 expression in vitro and cholesterol absorption in humans.
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PMID:Involvement of angiotensin II in intestinal cholesterol absorption. 2000 56

Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.
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PMID:Multidisciplinary pharmacotherapeutic options for nonalcoholic Fatty liver disease. 2330 32