Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abdominal aortic aneurysm is accompanied by the impairment of collagen metabolism in arterial wall. Metalloproteinases and collagen-stimulating factors play an important role in the maintenance of balance between collagen biosynthesis and degradation in tissues. Insulin-like growth factor-I (IGF-I) plays a major role in the stimulation of collagen biosynthesis. Its activity and bioavailability to target cells are modulated by IGF binding proteins (IGFBPs). The potential role of these factors in the mechanism of collagen metabolism deregulation in aortic aneurysm is the purpose of this study. Therefore, we have compared the content of collagen, gelatinolytic activity, IGF-I, IGFBP-1 and IGFBP-3 in normal human aorta and aortic aneurysm. The content of hydroxyproline (representing collagen content) in the proteins of aortic aneurysm was found to be similar to that found in normal aorta. Taking into account that some of the hydroxyproline may be derived from collagen degradation products (CDPs), they were separated and hydroxyproline was determined. It has been found that CDP-derived hydroxyproline content in aortic aneurysm was increased as compared with normal aorta, suggesting an increased collagen degradation. In contrast, zymography showed a decrease of collagenolytic activity in aortic aneurysm tissue, but an increase in mural thrombus, compared to respective controls. IGF-I concentration in aortic aneurysm was decreased, while the concentrations of BP-1 and BP-3 were both increased compared to control. The data suggest that increased collagen degradation in aortic aneurysm is due to the increase in collagenolytic activity in mural thrombus accompanying aneurysm tissue. It suggests that the mural thrombus may play a critical role in the pathogenesis of abdominal aortic aneurysm.
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PMID:Metalloproteinases, insulin-like growth factor-I and its binding proteins in aortic aneurysm. 1525 69

Low-glucose and -insulin conditions, associated with ketogenic diets, can reduce the activity of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, potentially leading to a range of positive medical and health-related effects. Here, we determined whether mTORC1 signaling is also a target for decanoic acid, a key component of the medium-chain triglyceride (MCT) ketogenic diet. Using a tractable model system, Dictyostelium, we show that decanoic acid can decrease mTORC1 activity, under conditions of constant glucose and in the absence of insulin, measured by phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). We determine that this effect of decanoic acid is dependent on a ubiquitin regulatory X domain-containing protein, mediating inhibition of a conserved Dictyostelium AAA ATPase, p97, a homolog of the human transitional endoplasmic reticulum ATPase (VCP/p97) protein. We then demonstrate that decanoic acid decreases mTORC1 activity in the absence of insulin and under high-glucose conditions in ex vivo rat hippocampus and in tuberous sclerosis complex (TSC) patient-derived astrocytes. Our data therefore indicate that dietary decanoic acid may provide a new therapeutic approach to down-regulate mTORC1 signaling.
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PMID:Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling. 3287 8