Disease relevance of Atherosclerosis

• To address a possible role of PLTP in dyslipidemia and atherogenesis, we bred mice deficient in the gene encoding PLTP (PLTP-deficient mice) using different hyperlipidemic mouse strains [1].
• The extracellular matrix on atherogenesis and diabetes-associated vascular disease [2].
• To determine if responses to gram-negative bacteria are necessary for atherogenesis, we first bred atherosclerosis-prone apolipoprotein (apo) E(-/)- (deficient) mice with animals incapable of responding to bacterial lipopolysaccharide [3].
• The clinical information is biologically plausible, as it is compatible with evidence that inhibition of COX-2-derived PGI2 removes a protective constraint on thrombogenesis, hypertension, and atherogenesis in vivo [4].
• The increased PAI-1 detected in the atheroma may contribute in vivo to accelerated or persistent thrombosis underlying acute occlusion and to vasculopathy exacerbated by clot-associated mitogens in the vessel wall [5].

Psychiatry related information on Atherosclerosis

• CONCLUSION: Presence of APOE epsilon4/* seems to increase the risk for dementia and AD independently of its effect on dyslipidemia and atherogenesis [6].
• The interaction of apoE with heparan sulfate proteoglycans plays an important role in lipoprotein remnant uptake and likely in atherogenesis and Alzheimer's disease [7].
• Class A macrophage scavenger receptor (SR-A) is one of the major receptors of macrophages and plays important roles in atherogenesis and host defense mechanisms [8].

High impact information on Atherosclerosis

• These observations raise the possibility that an impaired ABCA1 pathway contributes to the enhanced atherogenesis associated with common inflammatory and metabolic disorders [9].
• Cells cultured from human atheroma contained mRNAs for the PDGF A chain (16 of 17 isolates) but none (of 13) that encoded PDGF B chain (the c-sis proto-oncogene product) [10].
• We also show that nicotine accelerates the growth of tumor and atheroma in association with increased neovascularization [11].
• We have examined the effect of p53 inactivation on atherogenesis in apoE-knockout mice, an animal model for atherosclerosis [12].
• Here we determine whether interruption of CD40 signalling influences atherogenesis in vivo in hyperlipidaemic mice [13].

Chemical compound and disease context of Atherosclerosis

• Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL) [14].
• Malondialdehyde-altered protein occurs in atheroma of Watanabe heritable hyperlipidemic rabbits [15].
• Specific interaction of lysine, arginine-rich segments of the apoB-100 lipoproteins, LDL, IDL and Lp (a), with the negatively charged glycosaminoglycans (GAGs) of PGs cause retention of the lipoproteins, one of the initiation process of atherogenesis [2].
• Oxidative stress is implicated in atherogenesis, yet most clinical trials with antioxidants, particularly vitamin E, have failed to protect against atherosclerotic diseases [16].
• This indicates that estrogen attenuates atherogenesis in cholesterol-fed ovariectomized rabbits and that two commonly prescribed progestogens do not counteract the effect [17].

Biological context of Atherosclerosis

• Viral and bacterial pathogens have long been suspected to be modulators of atherogenesis; however, mechanisms linking innate immunity to cholesterol metabolism are poorly defined [18].
• In later stages of atherogenesis (26-wk cholesterol feeding) the degree of oxidative modification of the tissue lipids did increase but the share of specific lipoxygenase products was significantly lower, suggesting an increasing overlay of the specific lipoxygenase products by nonenzymatic lipid peroxidation [19].
• Thus, in addition to its effects on the hemostatic and adhesive properties of EC, TNF also promotes release of PDGF, which may serve to modulate proliferation of vascular SMC during wound healing, inflammation, and atherogenesis [20].
• To determine whether cell-mediated immunity influences atherogenesis, New Zealand White rabbits fed a cholesterol-supplemented diet (0.5% wt/wt) were treated with cyclosporin A (n = 20) or vehicle alone (n = 16) for 12 wk [21].
• The results suggest that M-CSF enhances net hydrolysis of CE by stimulating the two CE hydrolases to a greater extent than ACAT, and M-CSF may reduce the rate of atherogenesis [22].

Anatomical context of Atherosclerosis

• Furthermore, atheroma of mice treated with anti-CD40L antibody contained significantly fewer macrophages (64%) and T lymphocytes (70%), and exhibited decreased expression of vascular cell adhesion molecule-1 [13].
• Hence, the aim of this study was to test the effect of alpha tocopherol supplementation on monocyte function relevant to atherogenesis [23].
• Vascular cell adhesion molecule-1 and smooth muscle cell activation during atherogenesis [24].
• This work has contributed to an atherosclerosis paradigm: scavenger receptor-mediated oxidized lipoprotein uptake is required for foam cell formation and atherogenesis [25].
• The early colocalization of T cells and the potent immunostimulatory cytokine IFN-gamma to atherosclerotic lesions suggest that the immune system contributes to atherogenesis [26].

Gene context of Atherosclerosis

• However, the role of CD40 signalling in atherogenesis in vivo remains unknown [13].
• To test MCP-1's role in atherogenesis, low density lipoprotein (LDL) receptor-deficient mice were made genetically deficient for MCP-1 and fed a high cholesterol diet [27].
• In addition, stromelysin-3 mRNA and protein colocalized with CD40L and CD40 within atheroma [28].
• Indeed, human atheroma in situ expressed IL-18 and elevated levels of its receptor subunits, IL-18Ralpha/beta, compared with nondiseased arterial tissue [29].
• Apolipoprotein E (apo E)-deficient mice are severely hypercholesterolemic and develop advanced atheromas independent of diet [30].

Analytical, diagnostic and therapeutic context of Atherosclerosis

• Quantitative evaluation revealed that the atherogenesis is positively correlated with the serum level of cholesterol-rich VLDL/LDL particles [31].
• Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor [32].
• Although the importance of the MCP-1/CCR2 pathway in atherogenesis has been clarified, it remains unanswered whether postnatal blockade of the MCP-1 signals could be a unique site-specific gene therapy [33].
• Specific inhibition of this UPA domain may represent an attractive target for pharmacological interventions in atherogenesis and restenosis after angioplasty [34].
• The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function (brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment [35].

References