scholarly journals Role of matrix metalloproteinases in the pathogenesis of intracranial aneurysms

2019 ◽  
Vol 47 (1) ◽  
pp. E4 ◽  
Author(s):  
Xiaoran Zhang ◽  
William J. Ares ◽  
Philipp Taussky ◽  
Andrew F. Ducruet ◽  
Ramesh Grandhi
Keyword(s):  
Blood Flow ◽  
Matrix Metalloproteinases ◽  
Vascular Remodeling ◽  
Intracranial Aneurysms ◽  
Normal Function ◽  
Mechanical Forces ◽  
Significant Morbidity ◽  
Complex Interactions ◽  
Aneurysm Development

Intracranial aneurysms (IAs) are a result of complex interactions between biochemical and mechanical forces and can lead to significant morbidity if they rupture and cause subarachnoid hemorrhage. This review explores the role of matrix metalloproteinases (MMPs) in the pathogenesis and progression of IAs. In addition to providing a review of the normal function of MMPs, it is intended to explore the interaction between inflammation and abnormal blood flow and the resultant pathological vascular remodeling processes seen in the development and rupture of IAs. Also reviewed is the potential for the use of MMPs as a diagnostic tool for assessment of aneurysm development and progression.

The role of vascular remodeling and inflammation in the pathogenesis of intracranial aneurysms

2014 ◽  
Vol 21 (1) ◽  
pp. 28-32 ◽  
Author(s):  
David L. Penn ◽  
Samantha R. Witte ◽  
Ricardo J. Komotar ◽  
E. Sander Connolly
Keyword(s):  
Vascular Remodeling ◽  
Intracranial Aneurysms

scholarly journals Role of Matrix Metalloproteinases in Early Hypertensive Vascular Remodeling

Hypertension ◽  
2007 ◽  
Vol 50 (1) ◽  
pp. 212-218 ◽  
Author(s):  
Martin Flamant ◽  
Sandrine Placier ◽  
Caroline Dubroca ◽  
Bruno Esposito ◽  
Izolina Lopes ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Vascular Remodeling

scholarly journals Roles of Matrix Metalloproteinases in Flow-Induced Outward Vascular Remodeling

2009 ◽  
Vol 29 (9) ◽  
pp. 1547-1558 ◽  
Author(s):  
Ryo Ota ◽  
Chie Kurihara ◽  
Tsung-Ling Tsou ◽  
William L Young ◽  
Yerem Yeghiazarians ◽  
...  
Keyword(s):  
Blood Flow ◽  
Matrix Metalloproteinases ◽  
Carotid Artery ◽  
Knockout Mice ◽  
Common Carotid Artery ◽  
Vascular Remodeling ◽  
Luminal Diameter ◽  
Mmp Inhibitor ◽  
Doxycycline Treatment ◽  
Reduced Flow

Sustained hemodynamic stresses, especially high blood flow, result in flow-induced outward vascular remodeling. Our previous study showed that macrophage depletion reduced flow-induced outward remodeling of the rat common carotid artery, indicating that macrophages are critical in flow-induced outward vascular remodeling. Macrophage is known to release proteinases, including matrix metalloproteinases (MMPs). Degradation and loosening of extracellular matrix by MMPs may facilitate vascular remodeling. Therefore, we assessed the functions of MMPs in flow-induced outward vascular remodeling by using the flow-augmented common carotid artery model in mice. We validated that ligation of the left common carotid artery increased blood flow and luminal diameter of the right common carotid artery without significant change in blood pressure of mice. To assess the functions of MMPs in flow-induced outward vascular remodeling, we used doxycycline (broad-spectrum MMP inhibitor), SB-3CT (selective MMP inhibitor), MMP-9 knockout mice, and MMP-12 knockout mice. Although there was only a trend for doxycycline treatment to reduce flow-induced outward vascular remodeling, SB-3CT treatment significantly reduced flow-induced outward vascular remodeling. In addition, flow-induced outward vascular remodeling was significantly reduced in MMP-9 knockout mice, but not in MMP-12 knockout mice. These data revealed that MMPs, especially MMP-9, are critical in flow-induced outward vascular remodeling.

scholarly journals Role of Matrix Metalloproteinases (MMPs) and MMP Inhibitors on Intracranial Aneurysms (A Review Article)

2013 ◽  
Vol 1 (5) ◽  
pp. 100-103 ◽  
Author(s):  
Azam Maradni ◽  
Seyed Hasan Emamirazavi ◽  
Abbas Noruzi-javidan ◽  
Seyed Hamzeh Mousavi ◽  
Alireza Khoshnevisan
Keyword(s):  
Matrix Metalloproteinases ◽  
Intracranial Aneurysms ◽  
Review Article ◽  
Mmp Inhibitors

The role of MMP-2 and MMP-9 polymorphisms in sporadic intracranial aneurysms

2006 ◽  
Vol 105 (3) ◽  
pp. 418-423 ◽  
Author(s):  
Hariyadarshi Pannu ◽  
Dong H. Kim ◽  
Dongchuan Guo ◽  
Terri M. King ◽  
Grace Van Ginhoven ◽  
...  
Keyword(s):  
Vascular Remodeling ◽  
Intracranial Aneurysms ◽  
Caucasian Population ◽  
Gelatinase A ◽  
Ruptured Aneurysms ◽  
Increased Risk ◽  
Extracellular Matrix Components ◽  
Study Population ◽  
Matrix Components

Object Matrix metalloproteinases (MMPs) are a family of endopeptidases that mediate vascular remodeling by degrading extracellular matrix components, such as collagen and elastin. On the basis of accumulating evidence that implicates increased MMP-2 (gelatinase A) and MMP-9 (gelatinase B) amounts and activity in the pathogenesis of aneurysms, the authors investigated the genetic association between polymorphisms in MMP-2 and MMP-9 and sporadic intracranial aneurysms. Methods Eight polymorphisms located in MMP-2 and MMP-9 were genotyped, and the association of these variations with disease was assessed in a Caucasian population consisting of 125 patients with intracranial aneurysms and 234 ethnically matched healthy volunteers. Polymorphisms in the MMP-2 gene and the haplotypes generated from these polymorphisms were not associated with the occurrence of intracranial aneurysms. However, a polymorphism located in the 3′ untranslated region of MMP-9 showed a significant association with disease in the study population, with individuals carrying the TT genotype at increased risk for developing intracranial aneurysms (odds ratio 1.91, p = 0.005). Haplotypes containing the T allele of this polymorphism also showed a comparable association with disease. Similar results were obtained in an analysis of these polymorphisms in a subgroup of patients who presented with ruptured aneurysms. Conclusions The study findings support a role for MMP-9, but not MMP-2, in the pathogenesis of intracranial aneurysms.

scholarly journals Role of Matrix Metalloproteinases in Vascular Remodeling

2003 ◽  
Vol 10 (5) ◽  
pp. 275-282 ◽  
Author(s):  
Masafumi Kuzuya ◽  
Akihisa Iguchi
Keyword(s):  
Matrix Metalloproteinases ◽  
Vascular Remodeling

scholarly journals Biology of Intracranial Aneurysms: Role of Inflammation

2012 ◽  
Vol 32 (9) ◽  
pp. 1659-1676 ◽  
Author(s):  
Nohra Chalouhi ◽  
Muhammad S Ali ◽  
Pascal M Jabbour ◽  
Stavropoula I Tjoumakaris ◽  
L Fernando Gonzalez ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Intracranial Aneurysms ◽  
Clinical Problem ◽  
Vascular Wall ◽  
Expression Of Genes ◽  
Aneurysmal Dilation ◽  
Inflammatory Phenotype ◽  
Aneurysm Development ◽  
Precise Role

Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, and other humoral mediators. Furthermore, gene expression profiling of IA compared with control arteries has prominently featured differential expression of genes involved with immune response/inflammation. Preliminary data suggest that therapies targeting the inflammatory response may have efficacy in the future treatment of IA. Further investigation, however, is necessary to elucidate the precise role of inflammation in IA pathogenesis, which can be exploited to improve the prognosis of patients harboring IA.

scholarly journals Role of Matrix Metalloproteinases in Angiogenesis and Its Implications in Asthma

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Khuloud Bajbouj ◽  
Rakhee K. Ramakrishnan ◽  
Qutayba Hamid
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Vascular Remodeling ◽  
Proteolytic Enzymes ◽  
Airway Remodeling ◽  
Inflammatory Cells ◽  
Bioactive Molecules ◽  
Matrix Remodeling ◽  
Pathological Conditions

Asthma is a chronic airway disorder associated with aberrant inflammatory and remodeling responses. Angiogenesis and associated vascular remodeling are one of the pathological hallmarks of asthma. The mechanisms underlying angiogenesis in asthmatic airways and its clinical relevance represent a relatively nascent field in asthma when compared to other airway remodeling features. Matrix metalloproteinases (MMPs) are proteases that play an important role in both physiological and pathological conditions. In addition to facilitating extracellular matrix turnover, these proteolytic enzymes cleave bioactive molecules, thereby regulating cell signaling. MMPs have been implicated in the pathogenesis of asthma by interacting with both the airway inflammatory cells and the resident structural cells. MMPs also cover a broad range of angiogenic functions, from the degradation of the vascular basement membrane and extracellular matrix remodeling to the release of a variety of angiogenic mediators and growth factors. This review focuses on the contribution of MMPs and the regulatory role exerted by them in angiogenesis and vascular remodeling in asthma as well as addresses their potential as therapeutic targets in ameliorating angiogenesis in asthma.

The tendon — a homeostatic unit tuned to mechanical forces

1978 ◽  
Vol 36 (2) ◽  
pp. 658-659
Author(s):  
M. J. Merrilees ◽  
G. C. Gillard ◽  
M. H. Flint
Keyword(s):  
Biochemical Study ◽  
Normal Function ◽  
Flexor Digitorum Profundus ◽  
Mechanical Forces ◽  
Connective Tissues ◽  
Matrix Organization ◽  
Flexor Digitorum ◽  
And Control ◽  
Positively Charged

To determine the role of mechanical forces in the maintenance and control of cell and matrix organization of connective tissues, we have undertaken a morphological and biochemical study of the rabbit hind limb Flexor Digitorum Profundus (FDP), a single tissue which is subjected to both tensional and compressive forces during normal function. Like all tendons, the FDP is designed to transmit tensional forces, but as it passes below the ankle a segment in contact with the calcaneum and talus is subjected to additional compressive forces. In this region the anterior half of the tendon is thickened to form a lenticular shaped sesamoid-type pad (Fig. 1) where cell and matrix organization resembles fibro-cartilage.The tensional regions of the FDP are characterized by elongated, flanged fibroblastictype cells intimately surrounded by densely packed, positively charged, collagen fibrils of long periodicity (63 nm) (Figs. 2 & 3), and small amounts of proteoglycan (0. 15% dry wt. ), predominantly dermatan sulphate.

The role of disturbed blood flow in the development of pulmonary arterial hypertension: lessons from preclinical animal models

2013 ◽  
Vol 305 (1) ◽  
pp. L1-L14 ◽  
Author(s):  
Michael G. Dickinson ◽  
Beatrijs Bartelds ◽  
Marinus A. J. Borgdorff ◽  
Rolf M. F. Berger
Keyword(s):  
Blood Flow ◽  
Pulmonary Arterial Hypertension ◽  
Animal Models ◽  
Arterial Hypertension ◽  
Human Disease ◽  
Vascular Remodeling ◽  
Pulmonary Blood Flow ◽  
Current Knowledge ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vasoproliferative disorder characterized by the development of unique neointimal lesions, including concentric laminar intima fibrosis and plexiform lesions. Although the histomorphology of neointimal lesions is well described, the pathogenesis of PAH and neointimal development is largely unknown. After three decades of PAH pathobiology research the focus has shifted from vasoconstriction towards a mechanism of cancer-like angioproliferation. In this concept the role of disturbed blood flow is seen as an important trigger in the development of vascular remodeling. For instance, in PAH associated with congenital heart disease, increased pulmonary blood flow (i.e., systemic-to-pulmonary shunt) is an essential trigger for the occurrence of neointimal lesions and PAH development. Still, questions remain about the exact role of these blood flow characteristics in disease progression. PAH animal models are important for obtaining insight in new pathobiological processes and therapeutical targets. However, as for any preclinical model the pathophysiological mechanism and clinical course has to be comparable to the human disease that it mimics. This means that animal models mimicking human PAH ideally are characterized by: a hit recognized in human disease (e.g., altered pulmonary blood flow), specific vascular remodeling resembling human neointimal lesions, and disease progression that leads to right ventriclular dysfunction and death. A review that underlines the current knowledge of PAH due to disturbed flow is still lacking. In this review we will summarize the current knowledge obtained from PAH animal models associated with disturbed pulmonary blood flow and address questions for future treatment strategies for PAH.

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