LOX-1 deficiency increases ruptured abdominal aortic aneurysm via thinning of adventitial collagen.

Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a key mediator of inflammation and plays an important role in the pathogenesis of atherosclerosis. Conversely, LOX-1 deficiency has been shown to decrease inflammation and atherosclerosis, both of which have been proposed to contribute to abdominal aortic aneurysm (AAA) pathogenesis. However, the role of LOX-1 in AAA pathogenesis remains unknown. Here, we investigated the effects of Olr1 (which encodes LOX-1) deletion on angiotensin II (Ang II)-induced AAA in apolipoprotein E knockout (ApoE KO) mice to determine whether LOX-1 deficiency mitigates AAA development. To accomplish this, we used serial, non-invasive ultrasound assessment, which revealed that the incidence and expansion rate of AAA were similar regardless of Olr1 deletion. However, Olr1 deletion significantly increased severe AAAs, including ruptured AAAs resulting in death. Oil Red O staining of the harvested aortas showed that the extent of atheroma burden localized in aneurysmal lesions did not differ between LOX-1-deficient and control mice, suggesting that Olr1 deletion did not decrease atheroma burden in the aneurysmal wall. Further histopathological analysis revealed that aneurysmal lesions in LOX-1-deficient mice had fewer fibroblasts and myofibroblasts, as well as thinner adventitial collagen, although the degree of elastin fragmentation or disruption was similar between LOX-1-deficient and control mice. An in vitro study confirmed that the proliferation of adventitial fibroblasts collected from LOX-1-deficient mice was significantly attenuated despite Ang II stimulation. In conclusion, Olr1 deletion may not mitigate aneurysm development but rather increases the vulnerability of rupture by suppressing adventitial fibroblast proliferation and collagen synthesis.

• Authors: Kayo Takahashi, Jun Aono, Yasuhisa Nakao, Mika Hamaguchi, Chika Suehiro, Mie Kurata, Tomohisa Sakaue, Akemi Kakino, Tatsuya Sawamura, Katsuji Inoue, Shuntaro Ikeda, Jun Suzuki, Osamu Yamaguchi
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 46 Issue 1 Pg. 63-74 (01 2023) ISSN: 1348-4214 [Electronic] England
• PMID: 36385349 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.

Chemical References

• Angiotensin II
• Collagen
• Scavenger Receptors, Class E

Topics

• Animals
• Mice
• Angiotensin II (pharmacology)
• Aorta, Abdominal (pathology)
• Aortic Aneurysm, Abdominal (etiology, pathology)
• Atherosclerosis (complications)
• Collagen
• Disease Models, Animal
• Inflammation (complications)
• Mice, Inbred C57BL
• Plaque, Atherosclerotic
• Scavenger Receptors, Class E (genetics)
• Mice, Knockout, ApoE