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Updated: May 18, 2026
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Fibroblast growth factor-2 is required for vasa vasorum plexus stability in hypercholesterolemic mice.
Jessica I Mollmark1, Andrew J-H Park1, Justin Kim1
1Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.).
A fibroblast growth factor-2 (FGF-2)/perlecan complex stabilizes the vasa vasorum plexus in atherosclerosis. Elevated plasmin activity disrupts this complex, inhibiting vasa vasorum and plaque development.
Area of Science:
- Cardiovascular Biology
- Angiogenesis Research
- Atherosclerosis Pathophysiology
Background:
- Vasa vasorum (VV) are small blood vessels supplying the arterial wall, which become angiogenic in advanced atherosclerosis.
- Fibroblast growth factor-2 (FGF-2) is a key angiogenic factor in atherosclerotic plaques and adventitia, particularly in hypercholesterolemic mouse models.
- The precise role of FGF-2 in the formation of the distinct vasa vasorum network in atherosclerosis remains to be fully elucidated.
Purpose of the Study:
- To investigate the structural organization of vasa vasorum in hypercholesterolemic mice.
- To determine the relationship between vasa vasorum network formation and the distribution of FGF-2.
- To elucidate the molecular mechanisms underlying vasa vasorum plexus stability and its regulation by FGF-2 and plasmin.
Main Methods:
- Hypercholesterolemic low-density lipoprotein receptor-deficient/apolipoprotein B(100/100) (DKO) mice were treated with saline, recombinant plasminogen activator inhibitor-1(23) (rPAI-1(23)), or soluble FGF receptor 1.
- Vasa vasorum were visualized using fluorescein-labeled Lycopersicon esculentum lectin perfusion and confocal microscopy.
- FGF-2 distribution, vasa vasorum density and area, perlecan presence, and plasmin activity were quantified.
Main Results:
- Saline-treated DKO mice exhibited an angiogenic vasa vasorum plexus in the adventitia, mirroring the FGF-2 distribution pattern.
- Treatment with rPAI-1(23) or soluble FGF receptor 1 disrupted the plexus, significantly reducing FGF-2 and vasa vasorum density and area.
- A complex of FGF-2 and perlecan was identified as critical for plexus stability; excess plasmin degraded perlecan, destabilizing the network.
- Elevated plasmin activity correlated with reduced plaque size in DKO and DKO/plasminogen activator inhibitor-1(-/-) mice.
Conclusions:
- The stability of the vasa vasorum plexus in advanced atherosclerosis is dependent on an FGF-2/perlecan complex.
- Increased plasmin activity significantly inhibits the development of the vasa vasorum plexus and atherosclerotic plaques.
