Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mature extracellular matrix (ECM) is a heterogenous substance produced by a variety of cells, mostly of mesothelial origin. The ECM serves as a tissue skeleton, a medium of communication between cells and as a barrier between the cells and the vascular system. The matrix is continuously remodelled in the living tissues. A variety of proteases, including matrix metalloproteases (MMPs), contribute to matrix destruction. These proteases are neutralised by naturally occurring inhibitors such as alpha 2-macroglobulin or tissue inhibitors of metalloproteases (TIMPs). Proteases and their inhibitors are often produced by the same cells, thus matrix remodelling is localised and strictly controlled. The MMPs are zinc-endopeptidases functioning at a neutral pH and requiring ionised calcium for activity. The extracellular matrix is an essential part of every organ and tissue type. MMPs are the key components of the system that dynamically controls the structure and function of the ECM. MMPs have been implicated in corneal disease, periodontal disease, dermatological disorders, atherosclerosis, bone and joint disorders, fibrotic disease, vascular abnormalities, malignancy and many other pathological processes. Several synthetic inhibitors of MMPs have been developed and many of them are currently in clinical trials. Compounds discussed in this article include batismastat, marimastat, BAY12-9566, AG-3340, OPB-3206, KBR-7785, KBR-8301, CDP-845 (CT-1746), metastat and AE-941 (Neovastat).
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PMID:Clinical potential of matrix metalloprotease inhibitors. 1056 4

The gut microbiota is associated with cardiovascular diseases, including atherosclerosis. However, the composition, functional capacity, and metabolites of the gut microbiome about atherosclerosis have not been comprehensively studied. Here, we reanalyzed 25 metagenomic stool samples from Sweden and 385 metagenomic stool samples from China using HUMAnN2, PanPhlAn, and MelonnPan to obtain more sufficient information. We found that the samples from atherosclerotic patients in both cohorts were depleted in Bacteroides xylanisolvens, Odoribacter splanchnicus, Eubacterium eligens, Roseburia inulinivorans, and Roseburia intestinalis. At the functional level, healthy metagenomes were both enriched in pathways of starch degradation V, glycolysis III (from glucose), CDP-diacylglycerol biosynthesis, and folate transformations. R inulinivorans and R intestinalis are major contributors to starch degradation V, while E eligens greatly contribute to the pathway CDP-diacylglycerol biosynthesis, and B xylanisolvens and B uniformis contribute to folate transformations II. The 11 marker species selected from the Chinese cohort distinguish patients from controls with an area under the receiver operating characteristics curve (AUC) of 0.86. Strain-level microbial analysis revealed a geographically associated adaptation of the strains from E eligens, B uniformis, and E coli. Two gut microbial metabolites, nicotinic acid and hydrocinnamic acid, had significantly higher predicted abundance in the control samples compared to the patients in the Chinese cohort, and interestinglynicotinic acid is already an effective lipid-lowering drug to reducing cardiovascular risk. Our results indicate intestinal bacteria such as B xylanisolvens, E eligens, and R inulinivorans could be promising probiotics and potential therapeutic target for atherosclerosis.
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PMID:Metagenomic analysis of the gut microbiome in atherosclerosis patients identify cross-cohort microbial signatures and potential therapeutic target. 3293 80