The Molecular Mechanisms of the Thrombotic Complications of Atherosclerosis

Overview

Journal J Intern Med

Specialty General Medicine

Date 2008 Apr 16

PMID 18410595

Citations 70

Authors

P Libby

Affiliations

Soon will be listed here.

Abstract

Our evolving knowledge of the cellular and molecular mechanisms underlying atherosclerosis has helped uncover the underlying causes behind thrombotic complications of this disease. Most fatal coronary thrombosis result from fibrous cap rupture or superficial erosion. Recent research has established a role for matrix metalloproteinases in the regulation of aspects of plaque structure related to propensity to disrupt and provoke thrombosis. Inflammatory pathways impinge on proteinase activity and aspects of oxidative stress that may favour plaque disruption. Novel molecular imaging strategies may permit visualization of proteinase activity in vivo, providing a new functional window on pathophysiology.

Citing Articles

Nanoparticle-Directed Antioxidant Therapy Can Ameliorate Disease Progression in a Novel, Diet-Inducible Model of Coronary Artery Disease.

Su S, Chen Z, Ke Q, Kocher O, Krieger M, Kang P Arterioscler Thromb Vasc Biol. 2024; 44(12):2476-2488.

PMID: 39417229 PMC: 11602363. DOI: 10.1161/ATVBAHA.124.321030.

Avocado-derived extracellular vesicles loaded with ginkgetin and berberine prevent inflammation and macrophage foam cell formation.

Sharma S, Mahanty M, Rahaman S, Mukherjee P, Dutta B, Imran Khan M J Cell Mol Med. 2024; 28(7):e18177.

PMID: 38494843 PMC: 10945093. DOI: 10.1111/jcmm.18177.

Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.

Dai W, Zhang H, Lund H, Zhang Z, Castleberry M, Rodriguez M Science. 2023; 381(6661):eadh5207.

PMID: 37651538 PMC: 10697821. DOI: 10.1126/science.adh5207.

Addition of Resolvins D1 or E1 to Collagen Membranes Mitigates Their Resorption in Diabetic Rats.

Almogy M, Moses O, Schiffmann N, Weinberg E, Nemcovsky C, Weinreb M J Funct Biomater. 2023; 14(5).

PMID: 37233393 PMC: 10219424. DOI: 10.3390/jfb14050283.

Targeting long non-coding RNA NUDT6 enhances smooth muscle cell survival and limits vascular disease progression.

Winter H, Winski G, Busch A, Chernogubova E, Fasolo F, Wu Z Mol Ther. 2023; 31(6):1775-1790.

PMID: 37147804 PMC: 10277891. DOI: 10.1016/j.ymthe.2023.04.020.

References

Morrow D, de Lemos J, Sabatine M, Wiviott S, Blazing M, Shui A . Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial. Circulation. 2006; 114(4):281-8. DOI: 10.1161/CIRCULATIONAHA.106.628909. View

Libby P, Theroux P . Pathophysiology of coronary artery disease. Circulation. 2005; 111(25):3481-8. DOI: 10.1161/CIRCULATIONAHA.105.537878. View

Baldus S, Heeschen C, Meinertz T, Zeiher A, Eiserich J, Munzel T . Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003; 108(12):1440-5. DOI: 10.1161/01.CIR.0000090690.67322.51. View

Hansson G, Jonasson L, Holm J, Claesson-Welsh L . Class II MHC antigen expression in the atherosclerotic plaque: smooth muscle cells express HLA-DR, HLA-DQ and the invariant gamma chain. Clin Exp Immunol. 1986; 64(2):261-8. PMC: 1542359. View

Nikkari S, OBrien K, Ferguson M, Hatsukami T, Welgus H, Alpers C . Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis. Circulation. 1995; 92(6):1393-8. DOI: 10.1161/01.cir.92.6.1393. View

Jaffer F, Kim D, Quinti L, Tung C, Aikawa E, Pande A . Optical visualization of cathepsin K activity in atherosclerosis with a novel, protease-activatable fluorescence sensor. Circulation. 2007; 115(17):2292-8. DOI: 10.1161/CIRCULATIONAHA.106.660340. View

Dollery C, Owen C, Sukhova G, Krettek A, Shapiro S, Libby P . Neutrophil elastase in human atherosclerotic plaques: production by macrophages. Circulation. 2003; 107(22):2829-36. DOI: 10.1161/01.CIR.0000072792.65250.4A. View

Fabunmi R, Sukhova G, Sugiyama S, Libby P . Expression of tissue inhibitor of metalloproteinases-3 in human atheroma and regulation in lesion-associated cells: a potential protective mechanism in plaque stability. Circ Res. 1998; 83(3):270-8. DOI: 10.1161/01.res.83.3.270. View

Mach F, Schonbeck U, Bonnefoy J, Pober J, Libby P . Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor. Circulation. 1997; 96(2):396-9. DOI: 10.1161/01.cir.96.2.396. View

10.

Mackman N, Brand K, Edgington T . Lipopolysaccharide-mediated transcriptional activation of the human tissue factor gene in THP-1 monocytic cells requires both activator protein 1 and nuclear factor kappa B binding sites. J Exp Med. 1991; 174(6):1517-26. PMC: 2119026. DOI: 10.1084/jem.174.6.1517. View

11.

Liu J, Sukhova G, Sun J, Xu W, Libby P, Shi G . Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol. 2004; 24(8):1359-66. DOI: 10.1161/01.ATV.0000134530.27208.41. View

12.

Davies M, Woolf N, Rowles P, Pepper J . Morphology of the endothelium over atherosclerotic plaques in human coronary arteries. Br Heart J. 1988; 60(6):459-64. PMC: 1224883. DOI: 10.1136/hrt.60.6.459. View

13.

Sugiyama S, Okada Y, Sukhova G, Virmani R, Heinecke J, Libby P . Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. Am J Pathol. 2001; 158(3):879-91. PMC: 1850342. DOI: 10.1016/S0002-9440(10)64036-9. View

14.

Davies M . Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995. Circulation. 1996; 94(8):2013-20. DOI: 10.1161/01.cir.94.8.2013. View

15.

Libby P . Changing concepts of atherogenesis. J Intern Med. 2000; 247(3):349-58. DOI: 10.1046/j.1365-2796.2000.00654.x. View

16.

Warner S, FRIEDMAN G, Libby P . Regulation of major histocompatibility gene expression in human vascular smooth muscle cells. Arteriosclerosis. 1989; 9(3):279-88. DOI: 10.1161/01.atv.9.3.279. View

17.

Rajavashisth T, Liao J, Galis Z, Tripathi S, Laufs U, Tripathi J . Inflammatory cytokines and oxidized low density lipoproteins increase endothelial cell expression of membrane type 1-matrix metalloproteinase. J Biol Chem. 1999; 274(17):11924-9. DOI: 10.1074/jbc.274.17.11924. View

18.

Galis Z, Sukhova G, Lark M, Libby P . Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994; 94(6):2493-503. PMC: 330083. DOI: 10.1172/JCI117619. View

19.

Falk E, Shah P, Fuster V . Coronary plaque disruption. Circulation. 1995; 92(3):657-71. DOI: 10.1161/01.cir.92.3.657. View

20.

Libby P, Simon D . Inflammation and thrombosis: the clot thickens. Circulation. 2001; 103(13):1718-20. DOI: 10.1161/01.cir.103.13.1718. View