Arteriosclerosis Medical and Health News Headlines

Patterns of USPIO deposition in murine atherosclerosis.

Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):E157; author reply E158-9

Authors: Klug G, Bauer L, Bauer WR

PMID: 18716317 [PubMed - in process]

Patterns of USPIO Deposition in Murine Atherosclerosis.

Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):e158-e159

Authors: Morris JB, Olzinski AR, Jucker BM

PMID: 18716318 [PubMed - as supplied by publisher]

VEGF-B taken to our hearts: specific effect of VEGF-B in myocardial ischemia.

Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1575-6

Authors: Claesson-Welsh L

PMID: 18716319 [PubMed - in process]

Targeted increases in endothelial cell superoxide anion production stimulate eNOS-dependent nitric oxide production, not uncoupled eNOS activity.

Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1580-1

Authors: Xu H, Pritchard KA

PMID: 18716321 [PubMed - in process]

Is LDL-C passed its prime? The emerging role of non-HDL, LDL-P, and ApoB in CHD risk assessment.

Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1582-3

Authors: Davidson MH

PMID: 18716322 [PubMed - in process]

Mineral Surface in Calcified Plaque Is Like That of Bone. Further Evidence for Regulated Mineralization.

Arterioscler Thromb Vasc Biol. 2008 Aug 14;

Authors: Duer MJ, Friscic T, Proudfoot D, Reid DG, Schoppet M, Shanahan CM, Skepper JN, Wise ER

OBJECTIVE: Cell biological studies demonstrate remarkable similarities between mineralization processes in bone and vasculature, but knowledge of the components acting to initiate mineralization in atherosclerosis is limited. The molecular level microenvironment at the organic-inorganic interface holds a record of the mechanisms controlling mineral nucleation. This study was undertaken to compare the poorly understood interface in mineralized plaque with that of bone, which is considerably better characterized. METHODS AND RESULTS: Solid state nuclear magnetic resonance (SSNMR) spectroscopy provides powerful tools for studying the organic-inorganic interface in calcium phosphate biominerals. The rotational echo double resonance (REDOR) technique, applied to calcified human plaque, shows that this interface predominantly comprises sugars, most likely glycosaminoglycans (GAGs). In this respect, and in the pattern of secondary effects seen to protein (mainly collagen), calcified plaque strongly resembles bone. CONCLUSIONS: The similarity between biomineral formed under highly controlled (bone) and pathological (plaque) conditions suggests that the control mechanisms are more similar than previously thought, and may be adaptive. It is strong further evidence for regulation of plaque mineralization by osteo/chondrocytic vascular smooth muscle cells.

PMID: 18703777 [PubMed - as supplied by publisher]

Endothelial Cell PECAM-1 Promotes Atherosclerotic Lesions in Areas of Disturbed Flow in ApoE-Deficient Mice.

Arterioscler Thromb Vasc Biol. 2008 Aug 7;

Authors: Harry BL, Sanders JM, Feaver RE, Lansey M, Deem TL, Zarbock A, Bruce AC, Pryor AW, Gelfand BD, Blackman BR, Schwartz MA, Ley K

OBJECTIVE: Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) has recently been shown to form an essential element of a mechanosensory complex that mediates endothelial responses to fluid shear stress. The aim of this study was to determine the in vivo role of PECAM-1 in atherosclerosis. METHODS AND RESULTS: We crossed C57BL/6 Pecam1(-/-) mice with apolipoprotein E-deficient (Apoe(-/-)) mice. On a Western diet, Pecam1(-/-)Apoe(-/-) mice showed reduced atherosclerotic lesion size compared to Apoe(-/-) mice. Striking differences were observed in the lesser curvature of the aortic arch, an area of disturbed flow, but not in the descending thoracic or abdominal aorta. Vascular cell adhesion molecule-1 (VCAM-1) expression, macrophage infiltration, and endothelial nuclear NF-kappaB were all reduced in Pecam1(-/-)Apoe(-/-) mice. Bone marrow transplantation suggested that endothelial PECAM-1 is the main determinant of atherosclerosis in the aortic arch, but that hematopoietic PECAM-1 promotes lesions in the abdominal aorta. In vitro data show that siRNA-based knockdown of PECAM-1 attenuates endothelial NF-kappaB activity and VCAM-1 expression under conditions of atheroprone flow. CONCLUSIONS: These results indicate that endothelial PECAM-1 contributes to atherosclerotic lesion formation in regions of disturbed flow by regulating NF-kappaB-mediated gene expression.

PMID: 18688018 [PubMed - as supplied by publisher]

Site-Specific Targeting of Nanoparticle Prednisolone Reduces In-Stent Restenosis in a Rabbit Model of Established Atheroma.

Arterioscler Thromb Vasc Biol. 2008 Aug 7;

Authors: Joner M, Morimoto K, Kasukawa H, Steigerwald K, Merl S, Nakazawa G, John MC, Finn AV, Acampado E, Kolodgie FD, Gold HK, Virmani R

OBJECTIVE: TRM-484 is a novel drug consisting of nanoparticles of prednisolone with high affinity to chondroitin sulfate proteoglycans (CSPGs). This may allow for neointimal suppression via directed targeting to areas of injury at systemic concentrations low enough to avoid adverse side effects known to occur with oral delivery of steroids. METHODS AND RESULTS: Atherosclerotic New Zealand white Rabbits were implanted with bare metal stents and randomized to receive intravenous TRM-484 at doses of 1 mg/kg or 0.32 mg/kg starting at the day of stenting and continuing 3 times a week for the duration of the study. Control animals received empty liposomes (placebo) or saline infusion. Stented arterial segments were harvested at 42 days and processed for histomorphometry and immunohistochemistry. Tissue and plasma levels were determined along with confocal microscopic analysis to determine distribution of rhodamine-labeled TRM-484 at various time points. TRM-484 was exclusively observed at sites of stent-induced injury, with absence of drug in contralateral nonstented arteries. Tissue concentration of stented arteries exceeded that of contralateral nonstented arteries by 100-fold 24 hours after administration of 1 mg/kg TRM-484 and resulted in significant reduction of percent stenosis compared to saline and placebo treated rabbits (22.5+/-4.4 versus 31.0+/-8.4 and 29.5+/-8.1%, P<0.03). CONCLUSIONS: TRM-484 at doses of 1 mg/kg resulted in significant suppression of in-stent neointimal growth in atherosclerotic rabbits. Site-specific targeting by this nanoparticle steroid in injured atherosclerotic areas might be a valuable and cost-effective approach for the prevention of in-stent restenosis.

PMID: 18688017 [PubMed - as supplied by publisher]

Apolipoprotein A-I Tryptophan Substitution Leads to Resistance to Myeloperoxidase-Mediated Loss of Function.

Arterioscler Thromb Vasc Biol. 2008 Aug 7;

Authors: Peng DQ, Brubaker G, Wu Z, Zheng L, Willard B, Kinter M, Hazen SL, Smith JD

OBJECTIVE: Apolipoprotein A-I (apoAI) acts as an ABCA1-dependent acceptor of cellular phospholipids and cholesterol during the biogenesis of HDL, but this activity is susceptible to oxidative inactivation by myeloperoxidase. We tried to determine which residues mediated this inactivation and create an oxidant-resistant apoAI variant. METHODS AND RESULTS: Mass spectrometry detected the presence of tryptophan, methionine, tyrosine, and lysine oxidation in apoAI recovered from human atheroma. We investigated the role of these residues in the myeloperoxidase-mediated loss of apoAI activity. Site-directed mutagenesis and chemical modification were used to create variants of apoAI which were tested for ABCA1-dependent cholesterol acceptor activity and oxidative inactivation. We previously reported that tyrosine modification is not required for myeloperoxidase-induced loss of apoAI function. Lysine methylation did not alter the sensitivity of apoAI to myeloperoxidase, whereas site-specific substitution of apoAI methionine to valine increased the sensitivity of apoAI to myeloperoxidase. ApoAI tryptophan residues were identified as essential in apoAI function and oxidant sensitivity as substitution of all four apoAI tryptophan residues to leucine led to loss of function, but the conservative substitution to phenylalanine retained full function and was resistant to oxidative inactivation. CONCLUSIONS: Tryptophan modification of apoAI is primarily responsible for the myeloperoxidase-mediated loss of the cholesterol acceptor activity of apoAI.

PMID: 18688016 [PubMed - as supplied by publisher]

Changes in plasma lipid concentrations and risk of coronary artery disease in army veterans suffering from chronic posttraumatic stress disorder.

Croat Med J. 2008 Aug;49(4):506-14

Authors: Dzubur Kulenovic A, Kucukalic A, Malec D

Aim. To test the differences in serum lipid concentrations between veterans with chronic posttraumatic stress disorder (PTSD) and veterans without PTSD. Methods. We determined plasma lipid parameters and calculated risk factors for 50 veterans in the PTSD group and 50 veterans in the non-PTSD group. Trauma exposure, coping strategies, and quality of life were assessed with Life Stressor List, Manchester Short Assessment of Quality of Life Scale, and Folkman-Lazarus Coping Strategies Questionnaire. Results. There was no difference between the groups in the exposure to combat trauma. PTSD group had significantly lover education than non-PTSD group (10.6+/-1.8 vs 12.4+/-2.6 years, P=0.007) and lower monthly income per family member (euro67.8+/-51.3 vs euro281.9+/-208.2, P<0.001). PTSD group had significantly higher levels of all plasma lipid parameters (cholesterol: 6.54+/-1.24 vs 5.40+/-1.09 mmol/L, P<0.001; triglycerides: 2.55+/-0.68 vs 1.73+/-0.77 mmol/L, P<0.001; very low density lipoprotein-cholesterol: 1.14+/-0.32 vs 0.78+/-0.35 mmol/L, P<0.001; low density lipoprotein-cholesterol: 4.49+/-1.06 vs 3.46+/-0.93 mmol/L, P<0.001). High-density lipoprotein cholesterol concentration was significantly lower in PTSD group (0.96+/-0.18 vs 1.15+/-0.24 mmol/L, P<0.001). Established risk factor for arteriosclerosis (6.96+/-1.19 vs 4.71+/-0.88, P<0.001) and Adult Treatment Panel III ten years risk for coronary disease (19.44+/-7.27% vs 9.74+/-4.10%, P<0.001) were significantly higher in the PTSD group. Secondary traumatization was significantly more frequent in the PTSD group (3.8+/-5.7 vs 1.3+/-4.7 events; P<0.001). Conclusions. Chronic PTSD is associated with dyslipidemia, leading to an increased risk of coronary artery disease. Environmental factors and coping strategies should be considered as important factors for the occurrence and persistence of PTSD.

PMID: 18716998 [PubMed - in process]

Caution on the Interpretation of Plasma Fatty Acid Composition as a Proxy Marker for SCD1 Activity: Particular Implications for Using the 16:1/16:0 Ratio in QTL Studies Involving Hyperlipidemic Patients.

Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):e153

Authors: Lusis J, Mar-Heyming RA

PMID: 18650502 [PubMed - in process]

Macrophage function and its impact on atherosclerotic lesion composition, progression, and stability: the good, the bad, and the ugly.

Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1413-5

Authors: Dickhout JG, Basseri S, Austin RC

PMID: 18650503 [PubMed - in process]

Myocardin: dominant driver of the smooth muscle cell contractile phenotype.

Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1416-7

Authors: Parmacek MS

PMID: 18650504 [PubMed - in process]

HDL: close to our memories?

Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1418-20

Authors: Kontush A, Chapman MJ

PMID: 18650505 [PubMed - in process]