SciCombinator

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Journal: Arteriosclerosis, thrombosis, and vascular biology

59

Genome-wide association studies have linked variants at chromosome 10q23 with increased coronary artery disease risk. The disease-associated variants fall in LIPA, which encodes lysosomal acid lipase (LAL), the enzyme responsible for lysosomal cholesteryl ester hydrolysis. Loss-of-function mutations in LIPA result in accelerated atherosclerosis. Surprisingly, the coronary artery disease variants are associated with increased LIPA expression in some cell types. In this study, we address this apparent contradiction.

Concepts: Artery, Coronary artery disease, Lipase, Atherosclerosis, DNA, Cell

34

Although fruit and vegetable (F&V) consumption is associated with lower risk of coronary heart disease and stroke, its association with peripheral artery disease (PAD) is less certain. We, thus, sought to characterize F&V intake and investigate the association between F&V consumption and presence of PAD in a large community sample.

Concepts: Peripheral vascular disease, The Association, Coronary circulation, Artery, Atherosclerosis, Coronary artery disease, Heart disease, Heart

32

Currently prescribed antiplatelet drugs have 1 common side effect-an increased risk of hemorrhage and thrombocytopenia. On the contrary, bleeding defects associated with glycoprotein VI (GPVI) expression deficiency are usually slightly prolonged bleeding times. However, GPVI antagonists are lacking in clinic.

Concepts: Platelet

30

OBJECTIVE: To test whether equivalent energy expenditure by moderate-intensity (eg, walking) and vigorous-intensity exercise (eg, running) provides equivalent health benefits.Approach and Results-We used the National Runners' (n=33 060) and Walkers' (n=15 945) Health Study cohorts to examine the effect of differences in exercise mode and thereby exercise intensity on coronary heart disease (CHD) risk factors. Baseline expenditure (metabolic equivant hours per day [METh/d]) was compared with self-reported, physician-diagnosed incident hypertension, hypercholesterolemia, diabetes mellitus, and CHD during 6.2 years follow-up. Running significantly decreased the risks for incident hypertension by 4.2% (P<10(-7)), hypercholesterolemia by 4.3% (P<10(-14)), diabetes mellitus by 12.1% (P<10(-5)), and CHD by 4.5% per METh/d (P=0.05). The corresponding reductions for walking were 7.2% (P<10(-7)), 7.0% (P<10(-8)), 12.3% (P<10(-4)), and 9.3% (P=0.01). Relative to <1.8 METh/d, the risk reductions for 1.8 to 3.6, 3.6 to 5.4, 5.4 to 7.2, and ≥7.2 METh/d were as follows: (1) 10.0%, 17.7%, 25.1%, and 34.9% from running and 14.0%, 23.8%, 21.8%, and 38.3% from walking for hypercholesterolemia; (2) 19.7%, 19.4%, 26.8%, and 39.8% from running and 14.7%, 19.1%, 23.6%, and 13.3% from walking for hypertension; and (3) 43.5%, 44.1%, 47.7%, and 68.2% from running, and 34.1%, 44.2% and 23.6% from walking for diabetes mellitus (walking >5.4 METh/d excluded for too few cases). The risk reductions were not significantly different for running than walking for diabetes mellitus (P=0.94), hypercholesterolemia (P=0.06), or CHD (P=0.26), and only marginally greater for walking than running for hypercholesterolemia (P=0.04). CONCLUSIONS: Equivalent energy expenditures by moderate (walking) and vigorous (running) exercise produced similar risk reductions for hypertension, hypercholesterolemia, diabetes mellitus, and possibly CHD.

Concepts: Cushing's syndrome, Stroke, Metabolic syndrome, Hypercholesterolemia, Obesity, Myocardial infarction, Diabetes mellitus, Hypertension

28

Aberrant neutrophil activation occurs during the advanced stages of atherosclerosis. Once primed, neutrophils can undergo apoptosis or release neutrophil extracellular traps. This extracellular DNA exerts potent proinflammatory, prothrombotic, and cytotoxic properties. The goal of this study was to examine the relationships among extracellular DNA formation, coronary atherosclerosis, and the presence of a prothrombotic state.

Concepts: Monocyte, Atherosclerosis, Macrophage

28

Aldosterone (Aldo) is involved in arterial stiffness and heart failure, but the mechanisms have remained unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, plays an important role in inflammation, fibrosis, and heart failure. We investigated here whether Gal-3 is involved in Aldo-induced vascular fibrosis.

Concepts: Cholesterol, Heart, Aldosterone, Blood pressure, Blood vessel

28

OBJECTIVE: Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo and examined the molecular mechanisms of RA signaling during the calcification process in vitro. METHODS AND RESULTS: Using a combination of approaches, we defined calcific aortic valve disease pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular, and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated Sox9 repression and calcification is regulated by classical RA signaling and requires both RA and retinoid X receptors. CONCLUSIONS: Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of calcific aortic valve disease in the human population.

Concepts: Gene, In vitro, Aortic valve, Retinol, Valves, Valvular heart disease, Aortic valve stenosis, Vitamin A

28

Inhibitor of differention-3 (Id3) promotes B cells homing to the aorta and atheroprotection in Apoe(-/-) mice. We sought to determine the impact of loss of Id3 in the Ldlr((-/-)) mouse model of diet-induced atherosclerosis and identify novel Id3 targets in the vessel wall.

Concepts: Blood vessel, VCAM-1, Monocyte, Macrophage, Gene, Atherosclerosis

28

Macrophage endothelial lipase (EL) is associated with increased atherosclerosis and inflammation. Because of their anti-inflammatory properties we hypothesized that n-3 fatty acids, in contrast to saturated fatty acids, would lower macrophages and arterial EL and inflammatory markers.

Concepts: Blood vessel, Saturated fat, Immune system, Fat, Omega-3 fatty acid, Anti-inflammatory, Inflammation, Atherosclerosis

27

Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein 3-kinase and an AMP-activated protein kinase (AMPK) kinase in some cell types. Although TAK1(-/-) mice display defects in developmental vasculogenesis, the role of TAK1 in endothelial cells has not been investigated in detail.

Concepts: Protein kinase A, Endothelium, Protein kinases, Signal transduction, Gene, Angiogenesis, Enzyme, Adenosine triphosphate