Cholesterol-Lowering Treatment Is Associated With Improvement in Coronary Vascular Remodeling and Endothelial Function in Patients With Normal or Mildly Diseased Coronary Arteries

Background: Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We hypothesize that recovering optimal levels of vitD in an animal model of PAH previously depleted of vitD improves the hemodynamics, the endothelial dysfunction and the ionic remodeling. Methods: Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O2) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and randomly divided into two groups: (a) continued on vitD-free diet or (b) received an oral dose of 100,000 IU/Kg of vitD plus standard diet for three weeks. Hemodynamics, pulmonary vascular remodeling, pulmonary arterial contractility, and K+ currents were analyzed. Results: Recovering optimal levels of vitD improved endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the activity of TASK-1 potassium channels. However, vitD supplementation did not reduce pulmonary pressure and did not ameliorate pulmonary vascular remodeling and right ventricle hypertrophy. Conclusions: Altogether, these data suggest that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH.

Download Full-text

Exercise-induced vasomotion of angiographically normal and stenotic coronary arteries improves after cholesterol-lowering drug therapy with bezafibrate

Journal of the American College of Cardiology ◽

10.1016/0735-1097(95)00379-7 ◽

1995 ◽

Vol 26 (7) ◽

pp. 1615-1622 ◽

Cited By ~ 41

Author(s):

Christian Seiler ◽

Thomas Martin Suter ◽

Otto Martin Hess

Keyword(s):

Drug Therapy ◽

Coronary Arteries ◽

Cholesterol Lowering ◽

Lowering Drug ◽

Exercise Induced

Download Full-text

Abstract 12063: High-risk Plaque Co-localizes With Low Endothelial Shear Stress and Expansive Remodeling in Human Coronary Arteries: A 3D Optical Coherence Tomography Study

Circulation ◽

10.1161/circ.132.suppl_3.12063 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Yiannis S Chatzizisis ◽

Konstantinos Toutouzas ◽

Andreas A Giannopoulos ◽

Maria Riga ◽

Antonios P Antoniadis ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Shear Stress ◽

High Risk ◽

Coronary Arteries ◽

Vascular Remodeling ◽

Pool Size ◽

Optical Coherence ◽

Fibrous Cap ◽

Endothelial Shear Stress

Background: High risk plaque accounts for the majority of acute coronary events. Low endothelial shear stress (ESS) is a key factor of the natural history of atherosclerosis. The role of ESS in high risk plaque formation is not well studied in man. Hypothesis: To explore the association of low ESS with high risk plaque and to identify the ESS milieu and vascular remodeling response in high risk vs. non high risk plaque. Methods: 35 coronary arteries from 30 patients were 3D reconstructed with fusion of coronary angiography and optical coherence tomography (Fig A-D) . ESS was calculated in the 3D reconstructed arteries using computational fluid dynamics (Fig E) and classified into low, moderate and high in 3 mm long segments. In each segment: i) fibroatheromas were classified into high risk and non high risk based on fibrous cap thickness and lipid pool size ii) vascular remodeling was classified into constrictive, compensatory and expansive. Results: Fibroatheromas in low ESS segments had significantly thinner fibrous cap compared to high ESS segments (89±84 vs.138±83 μm, p<0.05). Lipid pool size was comparable across all ESS categories. The majority of low ESS segments co-localized with high risk plaques (29 vs. 9%, p<0.05), whereas the majority of high ESS co-localized with non high risk plaques (24 vs. 9%, p<0.05, Fig F ). Compensatory and expansive remodeling was the predominant remodeling response in low ESS segments containing high risk plaques. In non-stenotic fibroatheromas (expansive or compensatory remodeling) low ESS was predominantly associated with high risk plaques (29 vs. 3%, p<0.05) whereas high ESS was associated with non high risk plaques (Fig F) . Conclusions: Novel combined anatomic and functional imaging with 3D OCT showed that low ESS and non-constrictive remodeling are associated with high risk plaque in man. Further studies are needed to assess the role of ESS and vascular remodeling in high risk plaque rupture and precipitation of clinical outcomes.

Download Full-text