Vascular Extracellular Matrix Remodeling Research Articles

A collagen I derived matricryptin increases aorta vascular wall remodeling after induced thrombosis in mouse

Matricryptins are collagen fragments proteolytically released from the extracellular matrix (ECM) with biological activity that can regulate several processes involved in ECM remodeling. Vessel wall matrix reorganization after lesion is important to the recovery of vascular function. This study aimed to analyze the effect of the peptide p1158/59 (Lindsey, 2015) on thrombosis, neointimal formation, and vascular remodeling of C57BL6 mice abdominal aorta. We used a FeCl3 induced vascular injury mice model and analyzed thrombus size, neointima formation, gelatinase activities in situ, re-endothelization, and collagen fibers organization on the arterial wall using polarization microscopy. As result, we observed that 2 days after injury the treatment with p1158/59 increased thrombus size and gelatinase activity, vascular lesion and it did not recover the endothelium loss induced by the chemical injury. We also observed that the peptide increased neointima growth and collagen birefringence, indicating collagen fibers reorganization. It also promoted increased re-endothelization and decreased activity of gelatinases 14 days after injury. Thus, we conclude that the peptide p1158/59 impaired the initial thrombosis recovery 2 days after injury but was able to induce vascular ECM remodeling after 14 days, improving vessel re-endothelization, collagen fibers deposition, and organization.

Internal modulation of proteolysis in vascular extracellular matrix remodeling: role of ADAM metallopeptidase with thrombospondin type 1 motif 5 in the development of intracranial aneurysm rupture.

Intracranial aneurysms (IAs) are common cerebrovascular diseases that carry a high mortality rate, and the mechanisms that contribute to IA formation and rupture have not been elucidated. ADAMTS-5 (ADAM Metallopeptidase with Thrombospondin Type 1 Motif 5) is a secreted proteinase involved in matrix degradation and ECM (extracellular matrix) remodeling processes, and we hypothesized that the dysregulation of ADAMTS-5 could play a role in the pathophysiology of IA. Immunofluorescence revealed that the ADAMTS-5 levels were decreased in human and murine IA samples. The administration of recombinant protein ADAMTS-5 significantly reduced the incidence of aneurysm rupture in the experimental model of IA. IA artery tissue was collected and utilized for histology, immunostaining, and specific gene expression analysis. Additionally, the IA arteries in ADAMTS-5-administered mice showed reduced elastic fiber destruction, proteoglycan accumulation, macrophage infiltration, inflammatory response, and apoptosis. To further verify the role of ADAMTS-5 in cerebral vessels, a specific ADAMTS-5 inhibitor was used on another model animal, zebrafish, and intracranial hemorrhage was observed in zebrafish embryos. In conclusion, our findings indicate that ADAMTS-5 is downregulated in human IA, and compensatory ADAMTS-5 administration inhibits IA development and rupture with potentially important implications for treating this cerebrovascular disease.

Cysteine cathepsins are altered by flow within an engineered in vitro microvascular niche.

Throughout the process of vascular growth and remodeling, the extracellular matrix (ECM) concurrently undergoes significant changes due to proteolytic activity—regulated by both endothelial and surrounding stromal cells. The role of matrix metalloproteinases has been well-studied in the context of vascular remodeling, but other proteases, such as cysteine cathepsins, could also facilitate ECM remodeling. To investigate cathepsin-mediated proteolysis in vascular ECM remodeling, and to understand the role of shear flow in this process, in vitro microvessels were cultured in previously designed microfluidic chips and assessed by immunostaining, zymography, and western blotting. Primary human vessels (HUVECs and fibroblasts) were conditioned by continuous fluid flow and/or small molecule inhibitors to probe cathepsin expression and activity. Luminal flow (in contrast to static culture) decreases the activity of cathepsins in microvessel systems, despite a total protein increase, due to a concurrent increase in the endogenous inhibitor cystatin C. Observations also demonstrate that cathepsins mostly co-localize with fibroblasts, and that fibrin (the hydrogel substrate) may stabilize cathepsin activity in the system. Inhibitor studies suggest that control over cathepsin-mediated ECM remodeling could contribute to improved maintenance of in vitro microvascular networks; however, further investigation is required. Understanding the role of cathepsin activity in in vitro microvessels and other engineered tissues will be important for future regenerative medicine applications.

Vascular Extracellular Matrix Remodeling and Hypertension.

Significance: The vascular extracellular matrix (ECM) not only provides mechanical stability but also manipulates vascular cell behaviors, which are crucial for vascular function and homeostasis. ECM remodeling, which alters vascular wall mechanical properties and exposes vascular cells to bioactive molecules, is involved in the development and progression of hypertension. Recent Advances: This brief review summarized the dynamic changes in ECM components and their modification and degradation during hypertension and after antihypertensive treatment. We also discussed how alterations in the ECM amount, assembly, mechanical properties, and degradation fragment generation provide input into the pathological process of hypertension. Critical Issues: Although the relevance between ECM remodeling and hypertension has been recognized, the underlying mechanism by which ECM remodeling initiates the development of hypertension remains unclear. Therefore, the modulation of ECM remodeling on arterial stiffness and hypertension in genetically modified rodent models is summarized in this review. The circulating biomarkers based on ECM metabolism and therapeutic strategies targeting ECM disorders in hypertension are also introduced. Future Directions: Further research will provide more comprehensive understanding of ECM remodeling in hypertension by the application of matridomic and degradomic approaches. The better understanding of mechanisms underlying vascular ECM remodeling may provide novel potential therapeutic strategies for preventing and treating hypertension. Antioxid. Redox Signal. 34, 765-783.

Molecular Mechanisms Associated with Angiotensin-Converting Enzyme-Inhibitory Peptide Activity on Vascular Extracellular Matrix Remodeling

Objective: This paper aimed to investigate the molecular mechanisms associated with angiotensin-converting enzyme (ACE)-inhibitory peptide activity involved in vascular extracellular matrix (ECM) remodeling. Therefore, changes in collagen fibers, elastic fibers and laminin were assessed in the left common carotid artery (LCCA). Methods: We selected 10-week-old male spontaneously hypertensive rats to study the expression levels of matrix metalloproteinases (MMPs), transforming growth factor, angiotensin (Ang) II and nuclear factor (NF)-p65 in the wall of carotid arteries. Results: Compared to the control group, laminin expression was significantly increased (p < 0.05) in the vascular endothelium of the LAP (a homemade ACE-inhibitory peptide, named by ourselves) group, whereas the percentage of elastic/collagen fibers in the LCCA vascular area was significantly decreased (p < 0.0001) in the LAP group. Immune blots of MMP-2, MMP-9, NF-p65 and AngII were significantly reduced in the LCCA wall in the LAP group. Conclusion: Vascular ECM remodeling may be related to the inhibitory action of LAP on ECM deposition.

Correction

HomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 25, No. 4Correction Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection Originally published15 Mar 2018https://doi.org/10.1161/atvb.25.4.875Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:875This article corrects the followingVitamin D, Shedding Light on the Development of Disease in Peripheral ArteriesIn the January 2005 issue of Arteriosclerosis, Thrombosis, and Vascular Biology, in the Brief Review entitled “Vitamin D, Shedding Light on the Development of Disease in Peripheral Arteries” by Norman and Powell (Arterioscler Thromb Vasc Biol, 2005;25:39–46), there was a typographical error in the section entitled “Vitamin D and Peripheral Arterial Calcification.” On page 42, in the fourth line from the bottom of the left column, “… anatagonist (paricalcitol) improves survival… ” should have read “… agonist (paricalcitol) improves survival… ” Previous Back to top Next FiguresReferencesRelatedDetailsCited By Cai Z, Gong Z, Li Z, Li L and Kong W (2021) Vascular Extracellular Matrix Remodeling and Hypertension, Antioxidants & Redox Signaling, 10.1089/ars.2020.8110, 34:10, (765-783), Online publication date: 1-Apr-2021. Related articlesVitamin D, Shedding Light on the Development of Disease in Peripheral ArteriesP.E. Norman, et al. Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:39-46 April 2005Vol 25, Issue 4 Advertisement Article InformationMetrics https://doi.org/10.1161/atvb.25.4.875 Originally publishedMarch 15, 2018 PDF download Advertisement

Abstracts of literature

Abstracts of literature