Increased aortic stiffness and attenuated lysyl oxidase activity in obesity

Ju Yi Chen, Pei Jane Tsai, Haw Chih Tai, Ruei Lan Tsai, Yu Tzu Chang, Mei Chung Wang, Yu Wei Chiou, Ming Long Yeh, Ming Jer Tang, Chen Fuh Lam, Shu Chu Shiesh, Yi Heng Li, Wei Chuan Tsai, Chang Hua Chou, Li Jen Lin, Hua Lin Wu, Yau Sheng Tsai

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

OBJECTIVE: One potential mechanism through which obesity exerts adverse effects on the vascular system is by increasing aortic stiffness, a change known to be predictive of increased cardiovascular mortality. The aim of this study was to investigate the pathophysiology that links obesity to aortic stiffening. APPROACH AND RESULTS: Obese (ob/ob) mice were used to examine physical, morphological, and molecular changes in the aorta in response to obesity. ob/ob mice had increased aortic pulse wave velocity and tissue rigidity. ob/ob aorta exhibited decreases of lysyl oxidase (LOX) activity and cross-linked elastin, and increases of elastin fragmentation and elastolytic activity. The aortas of ob/ob mice were surrounded by a significant amount of proinflammatory and pro-oxidative perivascular adipose tissue. In vitro studies revealed that the conditioned medium from differentiated adipocytes or the perivascular adipose tissue of ob/ob mice attenuated LOX activity. Furthermore, inhibition of LOX in wild-type lean mice caused elastin fragmentation and induced a significant increase in pulse wave velocity. Finally, we found that obese humans had stiffer arteries and lower serum LOX levels than do normal-weight humans. CONCLUSION: Our results demonstrated that obesity resulted in aortic stiffening in both humans and mice, and established a causal relationship between LOX downregulation and aortic stiffening in obesity.

Original languageEnglish
Pages (from-to)839-846
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume33
Issue number4
DOIs
Publication statusPublished - 2013 Apr 1

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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