Strategies to achieve coronary arterial plaque stabilization

Rabbani, Ramin; Topol, Eric J.

doi:10.1016/s0008-6363(98)00279-x

Cited by 116 publications

(63 citation statements)

References 186 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most acute ischemic cardiac syndromes, such as myocardial infarction, unstable angina, and sudden cardiac death, are the result of atherosclerotic plaque rupture and subsequent thrombosis. [43][44][45][46][47] A delay in the resolution of the clot may lead to the presence of a prolonged thrombogenic site, which may serve as a nidus for further platelet accumulation and clot formation.…”

Section: Discussionmentioning

confidence: 99%

Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin

Majors

Sengupta

Willard

et al. 2002

ATVB

View full text Add to dashboard Cite

Objective-More than 70% of circulating homocysteine is disulfide-bonded to protein, but little is known about the specific proteins that bind homocysteine and their function as a consequence of homocysteine binding. Methods and Results-When human plasma was incubated with [35 S]L-homocysteine, most of the homocysteine bound to albumin. However, additional homocysteine-binding proteins were detected, and 1 of them comigrated with fibronectin. Treatment with 2-mercaptoethanol removed the bound homocysteine, demonstrating the involvement of disulfide bonding. In contrast, [35 S]L-cysteine did not bind to fibronectin. Purified fibronectin bound Ϸ5 homocysteine molecules per fibronectin dimer. SDS-PAGE of a limited trypsin digestion of homocysteinylated fibronectin showed that several tryptic fragments contained [35 S]homocysteine. Sequence analysis demonstrated that the fragments containing bound homocysteine had localized mainly to the C-terminal region, within and adjacent to the fibrin-binding domain. Homocysteinylation of fibronectin significantly inhibited its capacity to bind fibrin by 62% (PϽ0.005). In contrast, neither the binding of fibronectin to gelatin nor its capacity to serve as an attachment factor for aortic smooth muscle cells was affected. Key Words: homocysteine Ⅲ fibronectin Ⅲ fibrin Ⅲ atherosclerosis Ⅲ thrombosis H omocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. In healthy well-nourished individuals, homocysteine metabolism is efficient and regulated, and the concentration of plasma total homocysteine is usually Յ12 mol/L. 1 Inborn errors of homocysteine metabolism, drugs that interfere with homocysteine metabolism, deficiencies of folic acid, vitamin B 6 or vitamin B 12 , and certain disease states, such as chronic renal failure, increase plasma total homocysteine levels. 2 The homocystinurias are a heterogeneous group of autosomal recessive diseases caused by inborn errors of homocysteine metabolism. [3][4][5] Patients with untreated homocystinuria have severe hyperhomocysteinemia (50 to 500 mol/L) and lifethreatening premature cardiovascular disease. Thrombosis, with or without embolism, is the major cause of death. Postmortem studies show multiple thrombotic occlusions and widespread premature atherosclerosis with intimal thickening. However, even mild hyperhomocysteinemia (15 to 25 mol/L), regardless of the underlying cause, is a strong independent risk factor for occlusive vascular disease, as shown by numerous case-control and prospective studies involving thousands of subjects. 1,2,6 The mechanisms of homocysteine-induced atherosclerosis and thrombosis have not been fully elucidated. Conclusions-TheseIn normal individuals, Ͼ70% of circulating homocysteine is disulfide-bonded to plasma proteins. 7,8 The primary carrier of disulfide-bound homocysteine is albumin, 9 -12 but other proteins with accessible cysteine residues are also potential carriers. The binding of homocysteine to cysteine residues may disrupt normal protein structure and impair...

show abstract

Section: Discussionmentioning

confidence: 99%

Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin

Majors

Sengupta

Willard

et al. 2002

ATVB

View full text Add to dashboard Cite

show abstract

“…9,24,25 Th1 and Th17 cells are pro-inflammatory Th cell subsets that can induce the rupture of atheroma by secreting pro-inflammatory cytokines, such as IFN-c and IL-17A. [26][27][28][29] Th2 cells, which antagonize the effects of Th1 cells, are considered an anti-atherosclerotic Th cell subset. Treg cells suppress inflammatory cells by directly contacting or secreting suppressive cytokines, and they play a protective role in the pathogenesis of atherosclerosis.…”

Section: Figurementioning

confidence: 99%

The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome

Yao

et al. 2011

Cell Mol Immunol

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are a novel class of small, non-coding RNAs that play a significant role in both inflammatory and cardiovascular diseases. Immune cells, especially T helper (Th) cells, are critical in the development of atherosclerosis and the onset of acute coronary syndrome (ACS). To assess whether inflammation-related miRNAs (such as miR-155, 146a, 21, 125a-5p, 125b, 31) are involved in the imbalance of Th cell subsets in patients with ACS, we measured the expression of related miRNAs in patients with acute myocardial infarction (AMI), unstable angina (UA), stable angina (SA) and chest pain syndrome (CPS); analyzed the relationship between miRNA expression and the frequency of Th cell subsets; and observed the co-expression of miR-155 and IL-17A in peripheral blood mononuclear cells (PBMCs) of patients with ACS. The results showed that the expression of miR-155 in the PBMCs of patients with ACS was decreased by approximately 60%, while the expression of both miR-21 and miR-146a was increased by approximately twofold. The expression patterns of miRNAs in plasma correlated with those in PBMCs, except for miR-21, which was increased by approximately sixfold in the AMI group and showed no significant difference between the UA group and the CPS group. We also found that the expression of miR-155 inversely correlated with the frequency of Th17 cells (r520.896, P,0.01) and that miR-155 was co-expressed with IL-17A in patients with ACS. In conclusion, our study revealed the expression patterns of inflammation-related miRNAs in patients with ACS and found that miR-155 may be associated with Th17 cell differentiation.

show abstract

“…MMP activity is controlled by specific inhibitors (TIMPs); four members of the tissue inhibitor family have been identified: TIMP-1, -2, -3, and -4 [11,12]. Their overexpression reduces neointimal development in experimental models of vascular injury and may provide protection against plaque destabilization [13,14].…”

Section: Introductionmentioning

confidence: 99%

Different expression of MMPs/TIMP-1 in human atherosclerotic lesions. Relation to plaque features and vascular bed

et al. 2003

View full text Add to dashboard Cite

Background: Proteolytic imbalance might determine arterial remodeling and plaque destabilization in atherosclerotic vessels. The aim of this study was to examine differences in the patterns of metalloproteinases (MMPs) and MMP inhibitor (TIMP-1) expression in advanced human atheromas, both in relation to the plaque features and the vascular bed involved. Methods and results: Immunohistochemistry for MMP-1, -3, -9 and TIMP-1 as well as the collagen content were measured in vascular sections from patients undergoing peripheral revascularization (carotid n = 11, femoral n = 23) and aorto-coronary bypass surgery (mammary arteries n = 20, as controls). Increased expression of all MMPs was detected in atherosclerotic as compared with control sections (P<0.01). Aneurismal plaques showed a significant increase of MMP-1 and-3 and a reduction in total collagen (P<0.05) in relation to occlusive lesions. Calcification areas in atherosclerotic plaques were consistently associated with increased TIMP-1 expression (P<0.01). Finally, MMP-9 expression was higher in occlusive lesions from carotid than femoral arteries (P<0.01). Conclusions: Aneurysm lesions expressed higher MMP-1 and-3 expression than occlusive plaques, and MMP-9 was mainly detected in carotid as compared with femoral arteries. TIMP-1 was associated with arterial calcification. These differences in the MMPs/TIMP-1 expression might determine the evolution of advanced atherosclerotic plaques and contribute to its vulnerability.

show abstract

Strategies to achieve coronary arterial plaque stabilization

Cited by 116 publications

References 186 publications

Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin

Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin

The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome

Different expression of MMPs/TIMP-1 in human atherosclerotic lesions. Relation to plaque features and vascular bed

Contact Info

Product

Resources

About