Elevated expression of connective tissue growth factor, osteopontin and increased collagen content in human ascending thoracic aortic aneurysms

Abstract

Little is known about the molecular mechanisms of ascending thoracic aortic aneurysms (ATAAs). Abnormal extracellular matrix changes and variations of vascular smooth muscle cells (VSMCs) have been implicated in abdominal aortic aneurysm formation. Our objective was to investigate the alterations of collagen, stimulators of collagen synthesis and synthetic VSMCs in patients with ATAA. Surgical samples from ATAA were taken from 20 patients, and 18 control aortas were obtained during coronary artery bypass surgery. All aortic wall specimens were fixed for histology and immunohistochemistry for collagen, connective tissue growth factor (CTGF) and osteopontin. Realtime polymerase chain reaction was used to determine their mRNA expression. Histology and semi- quantitative analysis demonstrated that protein levels of collagen, CTGF and osteopontin significantly increased by 1.9-, 1.4- and 2.2-fold, respectively (P< 0.01 for all) in the ATAA group than in the control group. Similar results were shown in mRNA levels of type laland Illal collagen, CTGF and osteopontin. The protein levels of CTGF and osteopontin were positively correlated with aortic diameter (r= 0.67, r= 0.73; P< 0.01 for both). In conclusion, overexpression of aortic CTGF and synthetic VSMCs marker (osteopontin), which is likely to be responsible for elevated aortic collagen content, may provide a potential mechanism for aneurysmal enlargement.

Activation of endocannabinoid system is associated with persistent inflammation in human aortic aneurysm

“…Induction of CTGF, a major collagen-deposition related factor, was reported in vascular smooth muscle cells after oxidative burst in thoracic aneurysms ex vivo [10]. A recent study reported higher level of CTGF, osteopontin-1, and collagen in human thoracic aneurysms when compared to CABG controls without significant difference in incidence of hypertension or diabetes [23]. Their results are in contrast to our data, probably due to the differences in the control group.…”

MiR‐195 promotes abdominal aortic aneurysm media remodeling by targeting Smad3

“…Collagen III, maintaining tensile strength and overall rigidity of the aorta, was also increased in the AAA tissues, which was in agreement with the results demonstrated by Pei et al . and Meng et al …”

“…31 Additionally, our results presented that ectopic expression of miR-195 up-regulated expressions of OPN and collagen III. Collagen III, maintaining tensile strength and overall rigidity of the aorta, was also increased in the AAA tissues, which was in agreement with the results demonstrated by Pei et al 32 and Meng et al 33 . On the contrary, collagen III was indicated to be down-regulated in ascending aortic aneurysm wall.…”

Overexpression of MicroRNA-145 Promotes Ascending Aortic Aneurysm Media Remodeling through TGF-β1

“…Some reports show a decreased expression of collagen in ascending aortic aneurysm wall, 21,22 whereas others show increased amounts. 6,23 It appears that either increases or decreases in collagen may weaken the aortic wall. In this study, the amount of collagen III increased in the wall of the ascending aortic aneurysm.…”