Table 2.
In vivo pre-clinical studies assessing the effect of cyclooxygenases in vascular remodeling.
| Specie | Intervention | Preclinical model | Phenotype | Mechanism | Ref. |
|---|---|---|---|---|---|
| Mouse | Cox-1 deletion | Atherosclerosis (ApoE KO) Carotid ligation | ↓ Athero plaque formation ↓ Platelet-vessel wall interactions |
↓ TxBM ↓ PGIM |
46 |
| Mouse | Cox-1 inhibitor (SC-560) TP antagonist (BM-573) |
Atherosclerosis (Ldlr KO) | ↓ Athero plaque formation ↑ Plaque stability |
↓ TxBM ↓ Vascular inflammation (CD40L) |
47 |
| Mouse | Cox-1 inhibitor (SC-560) | Atherosclerosis (ApoE KO) | ↓ Athero plaque formation | ↓ TxBM ↓ Vascular inflammation (CD40L) ↓ Apoptosis (Bax) |
48 |
| Mouse | Cox-1 deletion Cox-1 inhibitor (SC-58560) Cox-2 deletion Cox-2 inhibitor (SC58236) |
Ang II infusion Ang II infusion |
↓ Hypotension ↑ Hypertension |
↑ Medullary PGI2 and PGE2 | 49 |
| Mouse | Bone marrow Cox-1 deletion | Atherosclerosis (ApoE KO or Ldlr KO) | ↑ Athero plaque formation | ↑ Cox-2 expression in macrophages | 50 |
| Mouse | Bone marrow Cox-1 deletion | Atherosclerosis (ApoE KO) | ↓ Athero plaque formation | ↓ Inflammation (IL-6, VCAM, P-selectin) | 51 |
| Mouse | Cox-1 deletion | Atherosclerosis (ApoE KO) | ↓ Athero plaque formation | 52 | |
| Mouse | Cox-2 inhibitor (MF-tricyclic) | Atherosclerosis (ApoE KO) | ↑ Athero plaque formation | 53 | |
| Mouse | Cox-2 inhibitor (MF-tricyclic) Sulindac | Atherosclerosis (ApoE KO) | No effect on athero plaque formation | 54 | |
| Mouse | Nimesulide Indomethacin |
Atherosclerosis (Ldlr KO) |
No effect on athero plaque formation ↓ Athero plaque formation |
↓ PGIM ↓ Inflammation (sICAM-1, MCP-1) ↓PGIM ↓TxBM |
55 |
| Mouse | Celecoxib | Atherosclerosis (ApoE KO) | No effect on advanced athero plaque formation | 56 | |
| Mouse | Rofecoxib Indomethacin Hematopoietic Cox-2 deletion |
Atherosclerosis (Ldlr KO) | ↓ Athero plaque formation | 57 | |
| Mouse | Rofecoxib Cox-2 inhibitor (NS-398) Indomethacin Hematopoietic Cox-2 deletion |
Atherosclerosis (ApoE KO) | ↓ Athero plaque formation | 58 | |
| Mouse | Celecoxib | Atherosclerosis (ApoE KO) | ↓ Athero plaque formation | ↓ Inflammation (ICAM-1, VCAM-1) | 59 |
| Mouse | Celecoxib Rofecoxib Naproxen |
Atherosclerosis (ApoE KO) | No effect on initiation and progression of atherosclerosis | 60 | |
| Mouse | Parecoxib | Atherosclerosis (ApoE KO) | ↑ Athero plaque stability | ↓ Inflammation (VSMCs, macrophages, collagen, MMPs) | 61 |
| Mouse | Postnatal Cox-2 deletion | Atherosclerosis (ApoE KO) | ↑ Athero plaque formation Normal BP | ↑ Inflammation (VSMCs, leukocytes) | 62 |
| Mouse | EC Cox-2 deletion VSMC Cox-2 deletion EC/VSMC Cox-2 deletion |
Atherosclerosis (Ldlr KO) | ↑ Athero plaque formation | ↑ Inflammation ↑ TxBM ↑ Cox-2 expression in macrophages |
63 |
| Mouse | Macrophage Cox-2 deletion T-cell (CD-4+) Cox-2 deletion |
Atherosclerosis (Ldlr KO) | ↓ Athero plaque formation No effect on atherogenesis |
↓ Inflammation ↑ Cox-2 expression in VSMCs |
64 |
| Mouse | Cox-2 deletion | LSD HSD |
↑ Hypertension ↑ Hypertension |
68 | |
| Mouse | COX-1>COX-2 | HSD | ↑ Hypertension | ↓ PGI2 in renal medulla | 69 |
| Mouse | EC/VSMC Cox-2 deletion |
HSD | ↑ Hypertension | ↓ PGIM ↓ NO |
70 |
Ang II, angiotensin II; Apoe, apolipoprotein E; Athero, atherosclerosis; BAX, Bcl-2 Associated X-protein; BP, blood pressure; Cox, cyclooxygenase; EC, endothelial cell; HSD, high salt diet; ICAM, intracellular adhesion molecule; IL-6, interleukin-6; Ldlr, low density lipoprotein receptor; LSD, low-salt diet; MMP, metalloproteinase; MCP-1, monocyte chemoattractant protein-1; NO, nitric oxide; PGI2, prostacyclin; PGIM, urinary prostacyclin metabolite; TxBM, urinary thromboxane metabolite; VCAM, vascular cell adhesion molecule; VSMC, vascular smooth muscle cell.