Mechanisms involved in extracellular matrix remodeling and arterial stiffness induced by hyaluronan accumulation

Autor: Hui Chen, Song Chai, Karen Axelgaard Lorentzen, Ulf Simonsen, Lise Wogensen, Carl Christian Danielsen
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Apolipoprotein E
medicine.medical_specialty
Vascular smooth muscle
Blotting
Western
Aorta
Thoracic
Mice
Transgenic
Vascular Remodeling
Matrix metalloproteinase
Muscle
Smooth
Vascular
Extracellular matrix
Mice
03 medical and health sciences
chemistry.chemical_compound
Vascular Stiffness
Adjuvants
Immunologic
Osteoprotegerin
Cell Movement
medicine.artery
Internal medicine
medicine
Animals
Hyaluronic Acid
Cells
Cultured
TSG-6
Extracellular Matrix Proteins
Aorta
Reverse Transcriptase Polymerase Chain Reaction
Cell Differentiation
Atherosclerosis
Extracellular Matrix
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Endocrinology
Gene Expression Regulation
chemistry
Low-density lipoprotein
Immunology
cardiovascular system
RNA
Female
Cardiology and Cardiovascular Medicine
Zdroj: Lorentzen, K A, Chai, S, Chen, H, Danielsen, C C, Simonsen, U & Wogensen, L 2016, ' Mechanisms involved in extracellular matrix remodeling and arterial stiffness induced by hyaluronan accumulation ', Atherosclerosis, vol. 244, pp. 195-203 . https://doi.org/10.1016/j.atherosclerosis.2015.11.016
ISSN: 0021-9150
DOI: 10.1016/j.atherosclerosis.2015.11.016
Popis: Background and aims Hyperglycemia induces hyaluronan (HA) accumulation in the vasculature. Excessive accumulation of HA around the vascular smooth muscle cells (VSMC) results in increased aortic stiffness and strength and accelerated atherosclerosis in ApoE − / − mice. We hypothesized that HA accumulation primes the vasculature for atherosclerosis by crosslinking and reorganizing the extracellular matrix (ECM) and by pushing VSMC differentiation towards a less mature phenotype. Methods Aortas from HAS-2 transgenic (Tg) mice and wild type mice were used for all experiments. Biomechanics and cross-sectional area measurements were performed before and after HA digestion. The vessel and ECM composition was examined by immunoblotting and electron microscopy. Primary VSMC cultures were examined by qPCR and thymidine incorporation. Results Tg mice aorta cross-sectional area was increased before (14%, p = 0.0148), but not after HA digestion (p = 0.3437). The increase in vessel stiffness (32%, p = 0.0217) and strength (31%, p = 0.0043) in the Tg aorta persisted after HA digestion. Crosslinking of HA by heavy chains from Inter-α-Inhibitor was increased (175%, p = 0.0006). The Tg VSMCs have the appearance of a synthetic phenotype supported by a 40% decrease in α-smooth muscle actin isoform X1 (p = 0.0296) and an increase in proliferation (63%, p = 0.0048) and osteoprotegerin production (133%, p = 0.0010) in cultured Tg VSMCs. Conclusions Our results show that induced HA accumulation is followed by increased HA crosslinking and create a shift in VSMC phenotype and proliferation. These findings may provide a mechanism for how hyperglycemia through HA accumulation prime the vascular wall for cholesterol and leucocyte accumulation and development of atherosclerosis.
Databáze: OpenAIRE
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