Abstract
Vasa vasorum (VV) neovascularization is a key feature of early atherosclerosis and adds substantial endothelial exchange-surface to the coronary vessel wall. Thus, it is conceivable that VV neovascularization favors the entry of pro-inflammatory and pro-atherosclerotic blood components into the coronary vessel wall. We sought to investigate the effects of Thalidomide (Th), a potent anti-angiogenic drug on vasa vasorum (VV) neovascularization, vessel wall inflammation, and neointima formation in early experimental atherosclerosis. Female domestic swine, 3 months old, were fed normal (N, n = 12) or high-cholesterol diet (HC, n = 12) for 3 months. In each group six pigs were randomized to 200 mg Thalidomide daily for the diet period (N + Th, HC + Th). LADs were scanned with micro-CT (20 μm cubic voxel size) to determine VV spatial density (#/mm2). Fresh-frozen coronary tissue was used for western blotting (VEGF, TNF-α, LOX-1, Iκβα and Gro-α) and electrophoretic mobility shift assay (EMSA, NFκβ). Treatment with Thalidomide preserved VV spatial density [2.7 ± 0.3 (N), 6.4 ± 0.7 (HC), 3.5 ± 0.8 (HC + Th), p = ns HC + Th vs. N] and inhibited the expression of VEGF, TNF-κ and LOX-1, but not NFκβ activity in the coronary vessel wall. Immunofluorescence analyses revealed co-localization of vWF but not SMA and NFκβ, TNF-α as well as VEGF in HC and HC + Th coronaries. Intima-media thickness was significantly inhibited in HC + Th compared to HC. Serum levels of hs-CRP and TNF-α did not differ among the groups. Our study supports a role of VV neovascularization in the development of and a therapeutic potential for anti-angiogenic intervention in early atherosclerosis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 695-706 |
| Number of pages | 12 |
| Journal | Basic Research in Cardiology |
| Volume | 104 |
| Issue number | 6 |
| DOIs | |
| State | Published - 2009 |
Fingerprint
Keywords
- Early atherosclerosis
- Inflammation
- Micro-CT
- Neovascularization
- Vasa vasorum
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
- Physiology
Cite this
Prevention of vasa vasorum neovascularization attenuates early neointima formation in experimental hypercholesterolemia. / Gössl, Mario; Herrmann, Joerg; Tang, Hui; Versari, Daniele; Galili, Offer; Mannheim, Dallit; Rajkumar, S Vincent; Lerman, Lilach O; Lerman, Amir.
In: Basic Research in Cardiology, Vol. 104, No. 6, 2009, p. 695-706.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prevention of vasa vasorum neovascularization attenuates early neointima formation in experimental hypercholesterolemia
AU - Gössl, Mario
AU - Herrmann, Joerg
AU - Tang, Hui
AU - Versari, Daniele
AU - Galili, Offer
AU - Mannheim, Dallit
AU - Rajkumar, S Vincent
AU - Lerman, Lilach O
AU - Lerman, Amir
PY - 2009
Y1 - 2009
N2 - Vasa vasorum (VV) neovascularization is a key feature of early atherosclerosis and adds substantial endothelial exchange-surface to the coronary vessel wall. Thus, it is conceivable that VV neovascularization favors the entry of pro-inflammatory and pro-atherosclerotic blood components into the coronary vessel wall. We sought to investigate the effects of Thalidomide (Th), a potent anti-angiogenic drug on vasa vasorum (VV) neovascularization, vessel wall inflammation, and neointima formation in early experimental atherosclerosis. Female domestic swine, 3 months old, were fed normal (N, n = 12) or high-cholesterol diet (HC, n = 12) for 3 months. In each group six pigs were randomized to 200 mg Thalidomide daily for the diet period (N + Th, HC + Th). LADs were scanned with micro-CT (20 μm cubic voxel size) to determine VV spatial density (#/mm2). Fresh-frozen coronary tissue was used for western blotting (VEGF, TNF-α, LOX-1, Iκβα and Gro-α) and electrophoretic mobility shift assay (EMSA, NFκβ). Treatment with Thalidomide preserved VV spatial density [2.7 ± 0.3 (N), 6.4 ± 0.7 (HC), 3.5 ± 0.8 (HC + Th), p = ns HC + Th vs. N] and inhibited the expression of VEGF, TNF-κ and LOX-1, but not NFκβ activity in the coronary vessel wall. Immunofluorescence analyses revealed co-localization of vWF but not SMA and NFκβ, TNF-α as well as VEGF in HC and HC + Th coronaries. Intima-media thickness was significantly inhibited in HC + Th compared to HC. Serum levels of hs-CRP and TNF-α did not differ among the groups. Our study supports a role of VV neovascularization in the development of and a therapeutic potential for anti-angiogenic intervention in early atherosclerosis.
AB - Vasa vasorum (VV) neovascularization is a key feature of early atherosclerosis and adds substantial endothelial exchange-surface to the coronary vessel wall. Thus, it is conceivable that VV neovascularization favors the entry of pro-inflammatory and pro-atherosclerotic blood components into the coronary vessel wall. We sought to investigate the effects of Thalidomide (Th), a potent anti-angiogenic drug on vasa vasorum (VV) neovascularization, vessel wall inflammation, and neointima formation in early experimental atherosclerosis. Female domestic swine, 3 months old, were fed normal (N, n = 12) or high-cholesterol diet (HC, n = 12) for 3 months. In each group six pigs were randomized to 200 mg Thalidomide daily for the diet period (N + Th, HC + Th). LADs were scanned with micro-CT (20 μm cubic voxel size) to determine VV spatial density (#/mm2). Fresh-frozen coronary tissue was used for western blotting (VEGF, TNF-α, LOX-1, Iκβα and Gro-α) and electrophoretic mobility shift assay (EMSA, NFκβ). Treatment with Thalidomide preserved VV spatial density [2.7 ± 0.3 (N), 6.4 ± 0.7 (HC), 3.5 ± 0.8 (HC + Th), p = ns HC + Th vs. N] and inhibited the expression of VEGF, TNF-κ and LOX-1, but not NFκβ activity in the coronary vessel wall. Immunofluorescence analyses revealed co-localization of vWF but not SMA and NFκβ, TNF-α as well as VEGF in HC and HC + Th coronaries. Intima-media thickness was significantly inhibited in HC + Th compared to HC. Serum levels of hs-CRP and TNF-α did not differ among the groups. Our study supports a role of VV neovascularization in the development of and a therapeutic potential for anti-angiogenic intervention in early atherosclerosis.
KW - Early atherosclerosis
KW - Inflammation
KW - Micro-CT
KW - Neovascularization
KW - Vasa vasorum
UR - http://www.scopus.com/inward/record.url?scp=70349652320&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349652320&partnerID=8YFLogxK
U2 - 10.1007/s00395-009-0036-0
DO - 10.1007/s00395-009-0036-0
M3 - Article
C2 - 19458984
AN - SCOPUS:70349652320
VL - 104
SP - 695
EP - 706
JO - Basic Research in Cardiology
JF - Basic Research in Cardiology
SN - 0300-8428
IS - 6
ER -