Myofibroblast Involvement in Glycosaminoglycan Synthesis and Lipid Retention during Coronary Repair

Abstract

Myofibroblasts of adventitial origin have been linked to neointimal formation and remodeling after coronary injury. Accordingly, the goal of this study was to examine whether myofibroblasts contribute to focal accumulation of glycosaminoglycans (GAGs) and lipids during coronary repair. GAG synthesis was assessed by ex vivo labeling of balloon-injured porcine coronary arteries with ¹⁴C-glucosamine. The synthesis of total GAGs transiently increased at 8 days in the normolipemic model (a 2.2-fold increase over baseline, p < 0.05). The majority of newly synthesized GAGs were sensitive to chondroitin ABC lyase (chondroitin/dermatan sulfate GAGs). Versican was localized to myofibroblast-rich regions in the adventitia and neointima [positive for α-smooth muscle (SM) actin, negative for h-caldesmon and SM myosin heavy chain]. In contrast, the adjacent SM-rich media showed no increase in versican expression. The association between injury-induced GAG accumulation and lipid retention was examined at 2 weeks after coronary injury in the hyperlipemic model. Lipid (Oil Red O) accumulated in the neointima and adventitia, but not in the adjacent media. Coronary repair under hyperlipemic conditions was associated with macrophage infiltration (19 ± 5 vs. 3 ± 2% of neointimal cells in normolipemic animals, p < 0.001) and increased neointimal formation (1.8 ± 0.5 vs. 1.0 ± 0.3 mm² in normolipemic animals, p < 0.01). In conclusion, this study demonstrated a transient increase in GAG synthesis following coronary injury. Chondroitin sulfate proteoglycans (e.g., versican) were rapidly synthesized by activated adventitial and neointimal cells which could contribute to early lipid retention in injured vessels.

Influence of hydrogel mechanical properties and mesh size on vocal fold fibroblast extracellular matrix production and phenotype

“…VFF are believed to transform into myofibroblasts in response to LP injury, and higher myofibroblast levels have been linked with increased collagen deposition [51]. Studies of lung and arterial tissue indicate that cell elastin [52] and GAG secretion [53] are also elevated with increasing myofibroblast phenotype. Furthermore, elevated VFF proliferation rates (fraction of cells expressing PCNA) were observed with increasing mesh size and decreasing modulus.…”

Pathological Finding of Sirolimus-Eluting Stent (SES) Restenosis Lesion With Black Hole Appearance on Intravascular Ultrasound

“…10,11 On the other hand, histologic assessment of tissue from a black hole showed predominance of hypocellular matrix with areas of proteoglycans. [12][13][14][15] The predominance of proteoglycans could be related to general vascular wound-healing delay, 16 which can occur as late as 2 year following SES implantation. 17 In the present case, restenosis occurred from 3 to 16 months after SES implantation.…”

Oxidative Stress and Lipid Retention in Vascular Grafts

“…33 Our previous studies have shown that vascular tissues rich in proliferating fibroblasts produced higher amounts of sulfated GAG and exhibited avid lipid retention compared with differentiated SMCs. 34 Thus, oxidative stress and the synthesis of matrix proteins, which retain LDL, may promote oxidative lipid modifications and create conditions promoting early onset of SVG atherogenesis. This study has important clinical implications, providing biological rationale for the use of arterial conduits for coronary revascularization.…”