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

At present there is no known treatment for established glomerulosclerosis or atherosclerosis. Since the principal lesion in glomerulosclerosis involves mesangial cells, a vascular smooth muscle cell, we searched for new therapeutic approaches affecting vascular smooth muscle function, especially with respect to modifying the turnover of extracellular matrix. We used mice transgenic for bovine growth hormone (bGH), since these mice develop end-stage renal disease due to progressive glomerulosclerosis. We previously showed that the subcutaneous injection of a non-anticoagulant heparin reduced glomerulosclerosis in bGH mice. Since injectable drugs are not a practical means of controlling glomerulosclerosis in humans, we assessed oral heparin-like compounds and found that oral pentosan polysulfate (PPS) reduced glomerulosclerosis in bGH mice at non-toxic doses. Because the positive therapeutic response in the bGH model could have been principally hormone-mediated, we examined other models of non-immune mediated glomerulosclerosis, including ROP Os/+ non-diabetic and diabetic mice. We found that an oral PPS (Elmiron), which is approved for other indications in humans, reduced sclerosis in all of these forms of chronic, progressive glomerulosclerosis. Based on the similarity of the cellular events in glomerulosclerosis and arteriosclerosis, we assessed the effect(s) of PPS in congenital (Watanabe rabbits) and induced (New Zealand White lipid-fed rabbits) models of arteriosclerosis. The extent and severity of the lesions was significantly reduced in both models by PPS treatment. Finally, we asked whether the proliferative and sclerotic lesion, which is the cause of vascular graft stenosis, might also respond to PPS treatment. To do this we cultured cells from the materials removed from stenotic arteriovenous grafts in hemodialysis patients. We found that PPS inhibits the proliferation and matrix production in a dose-dependent manner.
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PMID:Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis: treatment with oral heparinoids. 940 38

Ulcerative colitis, Crohn's disease and interstitial cystitis share many common features, the most important of which is a defect in the glycoaminoglycan (GAG) defensive barrier. This defect allows penetration of toxins causing localized inflammatory response, followed by fibrosis and distant pathological changes, together with a myriad of biochemical and immunological changes. The latter has caused confusion as to etiology of the aforementioned disorders. This hypothesis is somewhat supported by the fact that agents such as glucosamine and pentosan polysulphate (Elmiron) that replace the GAG layer, improve the conditions. The potential for extrapolation of this hypothesis to atherosclerosis and arthropathies exists. There is a great danger in modern medical research that if one misses the wood for the trees, one becomes hopelessly lost in the minutiae of research. At present, it is embarrassing that ulcerative colitis (UC), Crohn's (CR) and interstitial cystitis (IC) are the cause of a great deal of morbidity and occasionally mortality, yet after intensive research, the etiology and effective treatment eludes us. The research in the past has focused extensively on inflammatory response in the mucosal lining, and biochemical, infective and immunological changes in the serum. This has led to a vast array of research pathways that seem at the present time to be totally lost and, might I say, aimless in direction, as a cause for these conditions, that remain amongst the most imperically treated in modern medicine. Another possible syndrome in this class would be Reiter's, which has many features in common with the above. The basic tenet of a GAG deficiency hypothesis is that, as shown in Figure 1A, an intact GAG layer provides, firstly, a mechanical and electrostatic defence against penetration of infective agents, toxins, antigenic protein moieties, etc. and, secondly, the prevention of extravasation of body fluid components. A degraded GAG layer is the start of the disease cascade of the above group of illnesses.
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PMID:Glycoaminoglycan (GAG) deficiency in protective barrier as an underlying, primary cause of ulcerative colitis, Crohn's disease interstitial cystitis and possibly Reiter's syndrome. 1046 66