3 results on '"Ridwan RY"'
Search Results
2. The effect of the heart rate lowering drug Ivabradine on hemodynamics in atherosclerotic mice.
- Author
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Xing R, Moerman AM, Ridwan RY, Gaalen KV, Meester EJ, van der Steen AFW, Evans PC, Gijsen FJH, and Van der Heiden K
- Subjects
- Animals, Atherosclerosis pathology, Cardiovascular Agents pharmacology, Heart Rate drug effects, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, ApoE, Plaque, Atherosclerotic pathology, Stress, Mechanical, Atherosclerosis drug therapy, Disease Models, Animal, Heart Rate physiology, Hemodynamics, Ivabradine pharmacology, Plaque, Atherosclerotic prevention & control
- Abstract
The heart rate lowering drug Ivabradine was shown to improve cardiac outcome in patients with previous heart failure. However, in patients without heart failure, no beneficial effect of Ivabradine was observed. Animal studies suggested a preventive effect of Ivabradine on atherosclerosis which was due to an increase in wall shear stress (WSS), the blood flow-induced frictional force exerted on the endothelium, triggering anti-inflammatory responses. However, data on the effect of Ivabradine on WSS is sparse. We aim to study the effect of Ivabradine on (i) the 3D WSS distribution over a growing plaque and (ii) plaque composition. We induced atherosclerosis in ApoE
-/- mice by placing a tapered cast around the right common carotid artery (RCCA). Five weeks after cast placement, Ivabradine was administered via drinking water (15 mg/kg/day) for 2 weeks, after which the RCCA was excised for histology analyses. Before and after Ivabradine treatment, animals were imaged with Doppler Ultrasound to measure blood velocity. Vessel geometry was obtained using contrast-enhanced micro-CT. Time-averaged WSS during systole, diastole and peak WSS was subsequently computed. Ivabradine significantly decreased heart rate (459 ± 28 bpm vs. 567 ± 32 bpm, p < 0.001). Normalized peak flow significantly increased in the Ivabradine group (124.2% ± 40.5% vs. 87.3% ± 25.4%, p < 0.05), reflected by an increased normalized WSS level during systole (110.7% ± 18.4% vs. 75.4% ± 24.6%, p < 0.05). However, plaque size or composition including plaque area, relative necrotic core area and macrophage content were not altered in mice treated with Ivabradine compared to controls. We conclude that increased WSS in response to Ivabradine treatment did not affect plaque progression in a murine model.- Published
- 2018
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3. Extracellular matrix defects in aneurysmal Fibulin-4 mice predispose to lung emphysema.
- Author
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Ramnath NW, van de Luijtgaarden KM, van der Pluijm I, van Nimwegen M, van Heijningen PM, Swagemakers SM, van Thiel BS, Ridwan RY, van Vliet N, Vermeij M, Hawinkels LJ, de Munck A, Dzyubachyk O, Meijering E, van der Spek P, Rottier R, Yanagisawa H, Hendriks RW, Kanaar R, Rouwet EV, Kleinjan A, and Essers J
- Subjects
- Aged, Animals, Aorta drug effects, Aorta metabolism, Aorta pathology, Aortic Aneurysm metabolism, Cohort Studies, Disease Susceptibility, Down-Regulation drug effects, Female, Humans, Lipopolysaccharides pharmacology, Lung drug effects, Lung immunology, Lung metabolism, Lung pathology, Male, Matrix Metalloproteinases metabolism, Mice, Neutrophils enzymology, Pancreatic Elastase metabolism, Pulmonary Alveoli drug effects, Pulmonary Alveoli metabolism, Pulmonary Alveoli pathology, Signal Transduction drug effects, Transforming Growth Factor beta metabolism, alpha 1-Antitrypsin metabolism, Aortic Aneurysm complications, Aortic Aneurysm pathology, Extracellular Matrix metabolism, Extracellular Matrix Proteins deficiency, Extracellular Matrix Proteins metabolism, Pulmonary Emphysema complications
- Abstract
Background: In this study we set out to investigate the clinically observed relationship between chronic obstructive pulmonary disease (COPD) and aortic aneurysms. We tested the hypothesis that an inherited deficiency of connective tissue might play a role in the combined development of pulmonary emphysema and vascular disease., Methods: We first determined the prevalence of chronic obstructive pulmonary disease in a clinical cohort of aortic aneurysms patients and arterial occlusive disease patients. Subsequently, we used a combined approach comprising pathological, functional, molecular imaging, immunological and gene expression analysis to reveal the sequence of events that culminates in pulmonary emphysema in aneurysmal Fibulin-4 deficient (Fibulin-4(R)) mice., Results: Here we show that COPD is significantly more prevalent in aneurysm patients compared to arterial occlusive disease patients, independent of smoking, other clinical risk factors and inflammation. In addition, we demonstrate that aneurysmal Fibulin-4(R/R) mice display severe developmental lung emphysema, whereas Fibulin-4(+/R) mice acquire alveolar breakdown with age and upon infectious stress. This vicious circle is further exacerbated by the diminished antiprotease capacity of the lungs and ultimately results in the development of pulmonary emphysema., Conclusions: Our experimental data identify genetic susceptibility to extracellular matrix degradation and secondary inflammation as the common mechanisms in both COPD and aneurysm formation.
- Published
- 2014
- Full Text
- View/download PDF
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