33 research outputs found
Analysis of arterial intimal hyperplasia: review and hypothesis
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Despite a prodigious investment of funds, we cannot treat or prevent arteriosclerosis and restenosis, particularly its major pathology, arterial intimal hyperplasia. A cornerstone question lies behind all approaches to the disease: what causes the pathology? Hypothesis: I argue that the question itself is misplaced because it implies that intimal hyperplasia is a novel pathological phenomenon caused by new mechanisms. A simple inquiry into arterial morphology shows the opposite is true. The normal multi-layer cellular organization of the tunica intima is identical to that of diseased hyperplasia; it is the standard arterial system design in all placentals at least as large as rabbits, including humans. Formed initially as one-layer endothelium lining, this phenotype can either be maintained or differentiate into a normal multi-layer cellular lining, so striking in its resemblance to diseased hyperplasia that we have to name it "benign intimal hyperplasia". However, normal or "benign " intimal hyperplasia, although microscopically identical to pathology, is a controllable phenotype that rarely compromises blood supply. It is remarkable that each human heart has coronary arteries in which a single-layer endothelium differentiates earl
Procyanidins are potent inhibitors of LOX-1: a new player in the French Paradox
Lectin-like oxidized LDL receptor-1 (LOX-1) is an endothelial receptor for oxidized LDL (oxLDL) and plays multiple roles in the development of cardiovascular diseases. We screened more than 400 foodstuff extracts for identifying materials that inhibit oxLDL binding to LOX-1. Results showed that 52 extracts inhibited LOX-1 by more than 70% in cell-free assays. Subsequent cell-based assays revealed that a variety of foodstuffs known to be rich in procyanidins such as grape seed extracts and apple polyphenols, potently inhibited oxLDL uptake in Chinese hamster ovary (CHO) cells expressing LOX-1. Indeed, purified procyanidins significantly inhibited oxLDL binding to LOX-1 while other ingredients of apple polyphenols did not. Moreover, chronic administration of oligomeric procyanidins suppressed lipid accumulation in vascular wall in hypertensive rats fed with high fat diet. These results suggest that procyanidins are LOX-1 inhibitors and LOX-1 inhibition might be a possible underlying mechanism of the well-known vascular protective effects of red wine, the French Paradox
Zofenopril or irbesartan plus hydrochlorothiazide in elderly patients with isolated systolic hypertension untreated or uncontrolled by previous treatment: a double-blind, randomized study
OBJECTIVE: To compare zofenoprilâ+âhydrochlorothiazide (Zâ+âH) vs. irbesartanâ+âhydrochlorothiazide (Iâ+âH) efficacy on daytime SBP in elderly (>65 years) patients with isolated systolic hypertension (ISH), untreated or uncontrolled by a previous monotherapy.
METHODS: After a 1-week run-in, 230 ISH patients (office SBPââ„â140âmmHg and DBPâ<â90âmmHgâ+âdaytime SBPââ„â135âmmHg and daytime DBPâ<â85âmmHg) were randomized double-blind to 18-week treatment with Zâ+âH (30â+â12.5âmg) or Iâ+âH (150â+â12.5âmg) once daily, in an international, multicenter study. Z and I doses could be doubled after 6 and 12 weeks, and nitrendipine 20âmg added at 12 weeks in nonnormalized patients.
RESULTS: In the full analysis set (nâ=â216) baseline-adjusted average (95% confidence interval) daytime SBP reductions after 6 weeks (primary study end point) were similar (Pâ=â0.888) with Zâ+âH [7.7 (10.7, 4.6)âmmHg, nâ=â107] and Iâ+âH [7.9 (10.7, 5.0)âmmHg, nâ=â109]. Daytime SBP reductions were sustained during the study, and larger (Pâ=â0.028) with low-dose Zâ+âH at study end [16.2 (20.0, 12.5)âmmHg vs. 11.2 (14.4, 7.9)âmmHg Iâ+âH]. Daytime SBP normalization (<135âmmHg) rate was similar under Zâ+âH and Iâ+âH at 6 and 12 weeks, but more common under Zâ+âH at 18 weeks (68.2 vs. 56.0%, Pâ=â0.031). Both drugs equally reduced SBP in the last 6âh of the dosing interval and homogeneously reduced SBP throughout the 24âh. The proportion of patients reporting drug-related adverse events was low (Zâ+âH: 4.4% vs. Iâ+âH: 6.0%; Pâ=â0.574).
CONCLUSION: Elderly patients with ISH respond well to both low and high-dose Z or I combined with H