Back to Search
Start Over
Deficiency of IL12p40 (Interleukin 12 p40) Promotes Ang II (Angiotensin II)–Induced Abdominal Aortic Aneurysm
- Source :
- Arteriosclerosis, Thrombosis, and Vascular Biology. 39:212-223
- Publication Year :
- 2019
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2019.
-
Abstract
- Objective— Abdominal aortic aneurysm is caused by the accumulation of inflammatory cells in the aortic wall. Our recent studies demonstrated that inhibition of Notch signaling attenuates abdominal aortic aneurysm formation by shifting the macrophage balance towards anti-inflammatory (M2) phenotype. Using IL12p40 −/− (interleukin 12 p40) mice, we investigated the effects of M2-predominant macrophages on the development of abdominal aortic aneurysm. Approach and Results— Male (8–10 week-old) wild-type and IL12p40 −/− mice (n=15) on C57BL/6 background were infused with Ang II (angiotensin II, 1000 ng/kg per minute) by implanting osmotic pumps subcutaneously for 28 days. In the IL12p40 −/− mice, Ang II significantly increased the maximal intraluminal diameter (9/15) as determined by transabdominal ultrasound imaging. In addition, IL12p40-deletion significantly increased aortic stiffness in response to Ang II as measured by pulse wave velocity and atomic force microscopy. Histologically, IL12p40 −/− mice exhibited increased maximal external diameter of aorta and aortic lesions associated with collagen deposition and increased elastin fragmentation compared with wild-type mice infused with Ang II. Mechanistically, IL12p40 deficiency by siRNA (small interfering RNA) augmented the Tgfβ2 -mediated Mmp2 expression in wild-type bone marrow–derived macrophages without affecting the expression of Mmp9 . No such effects of IL12p40 deficiency on MMP2/MMP9 was observed in human aortic smooth muscle cells or fibroblasts. Depletion of macrophages in IL12p40 −/− mice by clodronate liposomes significantly decreased the maximal external diameter of aorta and aortic stiffness in response to Ang II as determined by imaging and atomic force microscopy. Conclusions— IL12p40 depletion promotes the development of abdominal aortic aneurysm, in part, by facilitating recruitment of M2-like macrophages and potentiating aortic stiffness and fibrosis mediated by Tgfβ2 .
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
030204 cardiovascular system & hematology
MMP9
Article
Mice
Transforming Growth Factor beta2
03 medical and health sciences
Vascular Stiffness
0302 clinical medicine
Aneurysm
Fibrosis
medicine.artery
Internal medicine
medicine
Animals
Aorta
biology
Interleukin-12 Subunit p40
Chemistry
Angiotensin II
Macrophages
medicine.disease
Abdominal aortic aneurysm
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
cardiovascular system
biology.protein
Matrix Metalloproteinase 2
Aortic stiffness
Collagen
Cardiology and Cardiovascular Medicine
Elastin
Aortic Aneurysm, Abdominal
Subjects
Details
- ISSN :
- 15244636 and 10795642
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Accession number :
- edsair.doi.dedup.....41db0ba22d951ca60aef6c70a65c7612