Vitamin D Receptor Deficiency and Low Vitamin D Diet Stimulate Aortic Calcification and Osteogenic Key Factor Expression in Mice

Low levels of 25-hydroxy vitamin D (25(OH)D) are associated with cardiovascular diseases. Herein, we tested the hypothesis that vitamin D deficiency could be a causal factor in atherosclerotic vascular changes and vascular calcification. Aortic root sections of vitamin D receptor knockout (VDR−/−) mice that were stained for vascular calcification and immunostained for osteoblastic differentiation factors showed more calcified areas and a higher expression of the osteogenic key factors Msx2, Bmp2, and Runx2 than the wild-type mice (P<0.01). Data from LDL receptor knockout (LDLR−/−) mice that were fed western diet with either low (50 IU/kg), recommended (1,000 IU/kg), or high (10,000 IU/kg) amounts of vitamin D3 over 16 weeks revealed increasing plasma concentrations of 25(OH)D (P<0.001) with increasing intake of vitamin D, whereas levels of calcium and phosphorus in plasma and femur were not influenced by the dietary treatment. Mice treated with the low vitamin D diet had more calcified lesions and a higher expression of Msx2, Bmp2, and Runx2 in aortic roots than mice fed recommended or high amounts of vitamin D (P<0.001). Taken together, these findings indicate vitamin D deficiency as a risk factor for aortic valve and aortic vessel calcification and a stimulator of osteogenic key factor expression in these vascular areas

Small coronary calcifications are not detectable by 64-slice contrast enhanced computed tomography

Recently, small calcifications have been associated with unstable plaques. Plaque calcifications are both in intravascular ultrasound (IVUS) and multi-slice computed tomography (MSCT) easily recognized. However, smaller calcifications might be missed on MSCT due to its lower resolution. Because it is unknown to which extent calcifications can be detected with MSCT, we compared calcification detection on contrast enhanced MSCT with IVUS. The coronary arteries of patients with myocardial infarction or unstable angina were imaged by 64-slice MSCT angiography and IVUS. The IVUS and MSCT images were registered and the arteries were inspected on the presence of calcifications on both modalities independently. We measured the length and the maximum circumferential angle of each calcification on IVUS. In 31 arteries, we found 99 calcifications on IVUS, of which only 47 were also detected on MSCT. The calcifications missed on MSCT (n = 52) were significantly smaller in angle (27° ± 16° vs. 59° ± 31°) and length (1.4 ± 0.8 vs. 3.7 ± 2.2 mm) than those detected on MSCT. Calcifications could only be detected reliably on MSCT if they were larger than 2.1 mm in length or 36° in angle. Half of the calcifications seen on the IVUS images cannot be detected on contrast enhanced 64-slice MSCT angiography images because of their size. The limited resolution of MSCT is the main reason for missing small calcifications

An Essential Role for Diet in Exercise-Mediated Protection against Dyslipidemia, Inflammation and Atherosclerosis in ApoE-/- Mice

Diet and exercise promote cardiovascular health but their relative contributions to atherosclerosis are not fully known. The transition from a sedentary to active lifestyle requires increased caloric intake to achieve energy balance. Using atherosclerosis-prone ApoE-null mice we sought to determine whether the benefits of exercise for arterial disease are dependent on the food source of the additional calories.Mice were fed a high-fat diet (HF) for 4.5 months to initiate atherosclerosis after which time half were continued on HF while the other half were switched to a high protein/fish oil diet (HP). Half of each group underwent voluntary running. Food intake, running distance, body weight, lipids, inflammation markers, and atherosclerotic plaque were quantified. Two-way ANOVA tests were used to assess differences and interactions between groups. Exercised mice ran approximately 6-km per day with no difference between groups. Both groups increased food intake during exercise and there was a significant main effect of exercise F((1,44) = 9.86, p<0.01) without interaction. Diet or exercise produced significant independent effects on body weight (diet: F(1,52) = 6.85, p = 0.012; exercise: F(1,52) = 9.52, p<0.01) with no significant interaction. The combination of HP diet and exercise produced a greater decrease in total cholesterol (F(1, 46) = 7.9, p<0.01) and LDL (F(1, 46) = 7.33, p<0.01) with a large effect on the size of the interaction. HP diet and exercise independently reduced TGL and VLDL (p<0.05 and 0.001 respectively). Interleukin 6 and C-reactive protein were highest in the HF-sedentary group and were significantly reduced by exercise only in this group. Plaque accumulation in the aortic arch, a marker of cardiovascular events was reduced by the HP diet and the effect was significantly potentiated by exercise only in this group resulting in significant plaque regression (F1, 49 = 4.77, p<0.05).In this model exercise is beneficial to combat dyslipidemia and protect from atherosclerosis only when combined with diet

The Rotterdam Study: 2012 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods