P1746 Promoter region polymorphisms of matrix metalloproteinases and their influence on plaque rupture

2003 ◽  
Vol 24 (5) ◽  
pp. 333
Author(s):  
J SMITH
Keyword(s):  
Matrix Metalloproteinases ◽  
Promoter Region ◽  
Plaque Rupture

scholarly journals Biomarkers of Carotid Stenosis

2021 ◽  
Vol 3 (1) ◽  
pp. 104-130
Author(s):  
Sergey G. Sсherbak ◽  
Tatyana A. Kamilova ◽  
Svetlana V. Lebedeva ◽  
Dmitry A. Vologzhanin ◽  
Alexander S. Golota ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Carotid Stenosis ◽  
Plaque Rupture ◽  
Early Recognition ◽  
Clinical Problem ◽  
Vascular Wall ◽  
Inflammatory Factors ◽  
Atherosclerotic Lesions ◽  
Important Clinical Problem ◽  
Definition Of

Early recognition of rupture-prone atherosclerotic lesions in patients with high-graded carotid stenosis is an important clinical problem for preventing ischemic stroke. Various pathophysiological mechanisms are responsible for the progression and instability of plaques, such as changes in lipid composition, infiltration by immunoinflammatory cells and degradation of the extracellular matrix of the vascular wall by matrix metalloproteinases, enhanced inflammatory response and plaque neovascularization. These features are the main cause of plaque rupture and, as a consequence, neurologic symptoms. Therefore, matrix metalloproteinases and inflammatory factors can serve as possible markers for patients with severe unstable stenosis of carotid arteries. Due to the heterogeneity of atherosclerotic lesions, only one biomarker is not enough to reliably predict the development of a stroke. The use of a combination of biomarkers is better correlated with clinical data and, therefore, exceeds the analysis of individual factors. To increase the overall sensitivity and specificity and more reliable diagnosis of stroke in patients with symptomatic and asymptomatic carotid stenosis, the biomarker panel should include independent biomarkers. Further preclinical experiments and clinical trials are needed to assess the significance and precise definition of the threshold levels of such biomarkers before they can be used in clinical practice.

Matrix Metalloproteinases: Implication in Vascular Matrix Remodelling during Atherogenesis

1998 ◽  
Vol 94 (2) ◽  
pp. 103-110 ◽  
Author(s):  
Shu Ye ◽  
Steve Humphries ◽  
Adriano Henney
Keyword(s):  
Matrix Metalloproteinases ◽  
Plaque Rupture ◽  
Matrix Deposition ◽  
Naturally Occurring ◽  
Extracellular Matrix Components ◽  
The Matrix ◽  
Preferential Binding ◽  
Artery Disease ◽  
Matrix Accumulation ◽  
Functional Analyses

1. The matrix metalloproteinases are a family of at least 16 zinc-dependent endopeptidases possessing catalytic activity against extracellular matrix components. Some members of this family have been implicated in vascular matrix remodelling in the pathogenesis of atherosclerosis. 2. A common, naturally occurring variant has been identified in the promoter of the stromelysin gene with one allele having a run of five adenosines (5A) and the other having six adenosines (6A). Functional analyses have shown that the 6A allele has a lower promoter activity than the 5A allele, which is probably attributable to preferential binding of a putative transcriptional repressor protein. 3. In patients with coronary artery disease, the 6A allele has been found to be associated with progression of atherosclerosis assessed by sequential quantitative angiography. 4. In conclusion, the matrix metalloproteinases may be over-expressed in certain locations in atherosclerotic plaques, which might contribute to local destruction of connective tissue and thus plaque rupture. In the majority of lesional areas, however, matrix synthesis is likely to outstrip matrix degradation, because matrix accumulation is a major feature of most atheromas. This imbalance favouring matrix deposition is likely to be exacerbated in individuals with the 6A6A genotype in whom stromelysin expression is lower due to the weaker stromelysin promoter.

Circulating and adipose tissue matrix metalloproteinases in cardiometabolic risk environments: pathophysiological aspects

2014 ◽  
Vol 17 (2) ◽  
Author(s):  
Gabriela Berg ◽  
Laura Schreier ◽  
Veronica Miksztowicz
Keyword(s):  
Adipose Tissue ◽  
Matrix Metalloproteinases ◽  
Plaque Rupture ◽  
Hormone Replacement ◽  
Protective Role ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Fat Tissue ◽  
Risk Environments ◽  
Tissue Matrix ◽  
Circulating Levels

AbstractMatrix metalloproteinases (MMPs) play an important role during physiological tissue remodeling in embryonic development and angiogenesis, as well as in pathophysiological conditions such as obesity and development and vulnerability of atherosclerotic plaque. Moreover, MMP circulating levels have emerged as potential biomarkers of cardiovascular disease. MMP expression and activity are regulated by different factors such as insulin resistance and obesity. Expanded fat tissue has been demonstrated to be an active organ, where MMPs also exert a role in adipogenesis, angiogenesis, and proliferation of extracellular matrix (ECM). However, the lack of association between adipose tissue and plasma levels of some MMPs, specifically MMP-2 and MMP-9, suggests that this tissue is not a major contributor to circulating gelatinases. MMPs are also co-expressed or co-repressed in response to inflammatory adipocytokines, like adiponectin and leptin. Adiponectin may also play a protective role in plaque rupture through selectively increasing the tissue inhibitor of metalloproteinase (TIMP) expression. Leptin induces the expression of MMP-2 activators as well as the expression of MMP-2, MMP-9, and TIMP-1 in different human cells. Furthermore, sex hormones also participate in MMP regulation. In postmenopausal women, hormone replacement therapy produces an increase in MMP activity, leading to a breakdown in ECM homeostasis and accelerated progression of vascular pathologies. Besides, in men, an inverse relationship between testosterone levels and MMP-2 activity has been described. It is still necessary to go forward in the study of MMPs in different metabolic situations to corroborate their role as vulnerable plaque biomarkers.

Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque Rupture

2005 ◽  
Vol 85 (1) ◽  
pp. 1-31 ◽  
Author(s):  
Andrew C. Newby
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Vessel Wall ◽  
Plaque Rupture ◽  
Coronary Thrombosis ◽  
Wall Stress ◽  
Intimal Thickening ◽  
Vessel Wall Thickness ◽  
Tissue Ischemia

Intimal thickening, the accumulation of cells and extracellular matrix within the inner vessel wall, is a physiological response to mechanical injury, increased wall stress, or chemical insult (e.g., atherosclerosis). If excessive, it can lead to the obstruction of blood flow and tissue ischemia. Together with expansive or constrictive remodeling, the extent of intimal expansion determines final lumen size and vessel wall thickness. Plaque rupture represents a failure of intimal remodeling, where the fibrous cap overlying an atheromatous core of lipid undergoes catastrophic mechanical breakdown. Plaque rupture promotes coronary thrombosis and myocardial infarction, the most prevalent cause of premature death in advanced societies. The matrix metalloproteinases (MMPs) can act together to degrade the major components of the vascular extracellular matrix. All cells present in the normal and diseased blood vessel wall upregulate and activate MMPs in a multistep fashion driven in part by soluble cytokines and cell-cell interactions. Activation of MMP proforms requires other MMPs or other classes of protease. MMP activation contributes to intimal growth and vessel wall remodeling in response to injury, most notably by promoting migration of vascular smooth muscle cells. A broader spectrum and/or higher level of MMP activation, especially associated with inflammation, could contribute to pathological matrix destruction and plaque rupture. Inhibiting the activity of specific MMPs or preventing their upregulation could ameliorate intimal thickening and prevent myocardial infarction.

Matrix metalloproteinases in vascular physiology and disease

Vascular ◽  
2012 ◽  
Vol 20 (4) ◽  
pp. 210-216 ◽  
Author(s):  
Suzanne A Siefert ◽  
Rajabrata Sarkar
Keyword(s):  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Plaque Rupture ◽  
Neointimal Hyperplasia ◽  
Vascular Diseases ◽  
Aortic Aneurysms ◽  
Vascular Pathology ◽  
Ecm Remodeling ◽  
Collateral Artery ◽  
Vascular Physiology

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that primarily degrade components of the extracellular matrix (ECM). Remodeling of the ECM by MMPs is important in both physiological and pathological processes, including organ generation/regeneration, angiogenesis, wound healing, inflammation and tumor growth. In the vasculature, MMPs play a role in beneficial processes such as angiogenesis, collateral artery formation and thrombus resolution. However, MMP expression is also implicated in the pathogenesis of vascular diseases such as atherosclerosis, aortic aneurysms, plaque rupture and neointimal hyperplasia after balloon angioplasty. Here, we review the structure, functions and roles of MMPs in both neovascularization and vascular pathology and discuss the potential of, and challenges that face, adapting MMPs as therapeutic targets in vascular disease.

Cytokine synergy, collagenases and cartilage collagen breakdown

2003 ◽  
Vol 70 ◽  
pp. 125-133 ◽  
Author(s):  
Tim E. Cawston ◽  
Jenny M. Milner ◽  
Jon B. Catterall ◽  
Andrew D. Rowan
Keyword(s):  
Matrix Metalloproteinases ◽  
Inflammatory Cytokines ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
And Cartilage ◽  
Pro Inflammatory Cytokines

We have investigated proteinases that degrade cartilage collagen. We show that pro-inflammatory cytokines act synergistically with oncastatin M to promote cartilage collagen resorption by the up-regulation and activation of matrix metalloproteinases (MMPs). The precise mechanisms are not known, but involve the up-regulation of c-fos, which binds to MMP promoters at a proximal activator protein-1 (AP-1) site. This markedly up-regulates transcription and leads to higher levels of active MMP proteins.

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