C-reactive protein deficiency ameliorates experimental abdominal aortic aneurysms

Abstract

BackgroundC-reactive protein (CRP) levels are elevated in patients with abdominal aortic aneurysms (AAA). However, it has not been investigated whether CRP contributes to AAA pathogenesis.MethodsCRP deficient and wild type (WT) male mice were subjected to AAA induction via transient intra-aortic infusion of porcine pancreatic elastase. AAAs were monitored by in situ measurements of maximal infrarenal aortic external diameters immediately prior to and 14 days following elastase infusion. Key AAA pathologies were assessed by histochemical and immunohistochemical staining procedures. The influence of CRP deficiency on macrophage activation was evaluated in peritoneal macrophages in vitro.ResultsCRP protein levels were higher in aneurysmal than that in non-aneurysmal aortas. Aneurysmal aortic dilation was markedly suppressed in CRP deficient (aortic diameter: 1.08 ± 0.11 mm) as compared to WT (1.21 ± 0.08 mm) mice on day 14 after elastase infusion. More medial elastin was retained in CRP deficient than in WT elastase-infused mice. Macrophage accumulation was significantly less in aneurysmal aorta from CRP deficient than that from WT mice. Matrix metalloproteinase 2 expression was also attenuated in CRP deficient as compared to WT aneurysmal aortas. CRP deficiency had no recognizable influence on medial smooth muscle loss, lymphocyte accumulation, aneurysmal angiogenesis, and matrix metalloproteinase 9 expression. In in vitro assays, mRNA levels for tumor necrosis factor α and cyclooxygenase 2 were reduced in lipopolysaccharide activated peritoneal macrophages from CRP deficient as compared to wild type mice.ConclusionCRP deficiency suppressed experimental AAAs by attenuating aneurysmal elastin destruction, macrophage accumulation and matrix metalloproteinase 2 expression.

The incidence rate and histological characteristics of intimal hyperplasia in elastase‐induced experimental abdominal aortic aneurysms in mice

“…In mice infused with PPE, abdominal aortic photography and outer diameter measurement were performed using a microscope camera during surgery (recorded as day 0 for baseline diameter) and 14 days after surgery. 21 , 22 , 23 If the diameter of the abdominal aorta dilated by more than 50% on day 14 after surgery, we assumed that AAA was successfully induced. 24 …”

Cellular, Molecular and Clinical Aspects of Aortic Aneurysm—Vascular Physiology and Pathophysiology

“…However, a decreased collagen level can weaken the arterial wall structure, leading to AAA formation [60]. A decrease in elastin content, disrupting the collagen-to-elastin ratio balance, may influence the pathogenesis of various types of aneurysm and other aortic diseases, including atherosclerosis [61,62]. The degeneration of ECM component shows regional heterogeneity on the circumference of the aneurysm [63].…”