ACE Inhibitor Quinapril Reduces the Arterial Expression of NF-κB-Dependent Proinflammatory Factors but not of Collagen I in a Rabbit Model of Atherosclerosis

• Published in: The American journal of pathology Vol. 153; no. 6; pp. 1825 - 1837
• Main Authors: Hernández-Presa, Miguel A., Bustos, Carmen, Ortego, Mónica, Tuñón, José, Ortega, Luis, Egido, Jesús
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.12.1998; American Society for Investigative Pathology
• Subjects: Antihypertensive agents; Biological and medical sciences; Cardiovascular system; Medical sciences; Pharmacology. Drug treatments; Regular; Immunohistochemistry; Quinapril; In situ; Cytokine; Rabbit; Reverse transcription; Cardiovascular disease; Inflammation; Hybridization; Lagomorpha; Vascular disease; Chemokine; Polymerase chain reaction; Pathology; Vertebrata; Mammalia; Atherosclerotic plaque; Animal; Collagen; Atherosclerosis; Antihypertensive agent; Molecular biology; Mechanism of action; ACE inhibitor
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)65697-0

Increasing evidence supports an association between inflammation and plaque rupture. Macrophages and vascular smooth muscle cells are a source of cytokines and growth factors, which contribute to ongoing inflammation during atherogenesis. In a rabbit model of atherosclerosis, we evaluated the effect of the ACE inhibitor quinapril on different parameters implicated in the pathogenesis of the plaque, such as the presence of chemokines (interleukin-8, monocyte chemoattractant protein-1), collagen I, and vascular smooth muscle cell proliferation (PDGF-B). Since nuclear factor κB (NF-κB) has been implicated in the control of chemokine transcription and cell proliferation, we also investigated its activation and localization in the lesion. Quinapril administration for 28 days caused a down-regulation in arterial expression of interleukin-8 and monocyte chemoattractant protein-1 (mRNA and protein). However, collagen I expression (mRNA and protein) was not modified. PDGF-B expression was reduced in both the intima and the media. Active NF-κB, found in both macrophages and vascular smooth muscle cells, was also reduced by quinapril. Nevertheless, no significant changes were noted in the mild neointima formation, although a certain trend toward normalization was found in the quinapril-treated group. In conclusion, our results show that quinapril treatment attenuates several parameters associated with inflammation within the atherosclerotic lesions that are controlled by NF-κB, although it has no effect on collagen I expression. Both effects could contribute to the stabilization of the atherosclerotic plaque.