A Disintegrin and Metalloprotease 17 Mediates Neointimal Hyperplasia in Vasculature

Takaguri, Akira; Kimura, Keita; Hinoki, Akinari; Bourne, Allison; Autieri, Michael V.; Eguchi, Satoru

doi:10.1161/hypertensionaha.110.166892

Cited by 29 publications

(29 citation statements)

References 38 publications

(46 reference statements)

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“…A recent study showed that CaCl 2 -induced AAA did not develop in mice with inducible ADAM17 silencing [13]. Two major ADAM17 substrates likely mediating vascular remodeling are HB-EGF and TNF-α [11]. Our data demonstrated that EGFR activation is associated with AAA.…”

Section: Discussionmentioning

confidence: 49%

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Caveolin 1 is critical for abdominal aortic aneurysm formation induced by angiotensin II and inhibition of lysyl oxidase

et al. 2014

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Although angiotensin II (Ang II) and its receptor AT1 have been implicated in abdominal aortic aneurysm (AAA) formation, the proximal signaling events primarily responsible for AAA formation remain uncertain. Caveolae are cholesterol-rich membrane microdomains that serve as a signaling platform to facilitate the temporal and spatial localization of signal transduction events including those stimulated by Ang II. Caveolin-1 (Cav1) enriched caveolae in vascular smooth muscle cells mediate ADAM17-dependent epidermal growth factor receptor (EGFR) transactivation, which is linked to vascular remodeling induced by Ang II. Here, we have tested our hypothesis that Cav1 plays a critical role for development of AAA at least in part via its specific alteration of Ang II signaling within caveolae. Cav1−/− mice and the control wild-type mice were co-infused with Ang II and β-aminopropionitrile to induce AAA. We found that Cav1−/− mice with the co-infusion did not develop AAA compared to control mice in spite of hypertension. We found an increased expression of ADAM17 and enhanced phosphorylation of EGFR in AAA. These events were markedly attenuated in Cav1−/− aortae with the co-infusion. Furthermore, Cav1−/− mice aortae with the co-infusion showed less endoplasmic reticulum stress, oxidative stress and inflammatory responses compared to aortae from control mice. Cav1 silencing in cultured vascular smooth muscle cells prevented Ang II-induced ADAM17 induction and activation. In conclusion, Cav1 appears to play a critical role in the formation of AAA and associated endoplasmic reticulum/oxidative stress presumably through the regulation of caveolae compartmentalized signals induced by Ang II.

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Section: Discussionmentioning

confidence: 49%

“…This process relies on ADAM17 compartmentalization in caveolae and is crucial for vascular remodeling [10, 11]. In human AAA as well as in a mouse model where AAA is induced by aortic CaCl 2 application, significant up-regulation of ADAM17 has been reported [12].…”

Section: Introductionmentioning

confidence: 99%

Caveolin 1 is critical for abdominal aortic aneurysm formation induced by angiotensin II and inhibition of lysyl oxidase

et al. 2014

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“…Although we have not explored ADAM17 protease activity directly in vivo it is conceivable that the increase of its substrates in the circulation depends from increased enzymatic activity at local inflammatory sites. Therefore, to study ADAM17 activity in an atherosclerotic setting we decided to evaluate, among its many substrates [12,13], those that were already independently implicated in severity or complications of atherosclerosis [14], but never with a combined approach. We reasoned that local over-activity of ADAM17 may weaken atherosclerotic plaque, causing their rupture, as a consequence of enzyme activation promoted by well known cardiovascular risk factors such as hyperglycemia, hyperinsulinemia and oxidized LDL and consequent increase in intraplaque inflammatory cells trafficking [7,14e16].…”

Section: Discussionmentioning

confidence: 99%

A score including ADAM17 substrates correlates to recurring cardiovascular event in subjects with atherosclerosis

et al. 2015

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a b s t r a c tObjective: Atherosclerosis disease is a leading cause for mortality and morbidity. The narrowing/rupture of a vulnerable atherosclerotic plaque is accountable for acute cardiovascular events. However, despite of an intensive research, a reliable clinical method which may disclose a vulnerable patient is still unavailable.Approach and results: We tested the association of ADAM17 (A Disintegrin and Metallo Protease Domain 17) circulating substrates (sICAM-1, sVCAM-1, sIL6R and sTNFR1) with a second major cardiovascular events [MACEs] (cardiovascular death, peripheral artery surgeries, non-fatal myocardial infarction and non-fatal stroke) in 298 patients belonging to the Vascular Diabetes (AVD) study. To evaluate ADAM17 activity we create ADAM17 score through a RECPAM model. Finally we tested the discrimination ability and the reclassification of clinical models. At follow-up (mean 47 months, range 1e118 months), 55 MACEs occurred (14 nonfatal MI, 14 nonfatal strokes, 17 peripheral artery procedures and 10 cardiovascular deaths) (incidence ¼ 7.8% person-years). An increased risk for incident events was observed among the high ADAM17 score individuals both in univariable (HR 19.20, 95% CI 15.82e63.36, p < 0.001) and multivariable analysis (HR 3.42, 95% CI 1.55 e7.54, p < 0.001). Finally we found that ADAM17 score significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement ¼ 9%, p ¼ 0.012) and correctly reclassifying 10% of events and 41% of non-events resulting in a cNRI ¼ 0.51 (p ¼ 0.005). Conclusion: We demonstrated a positive role of ADAM17 activity to predicting CV events. We think that an approach that targets strategies beyond classic cardiovascular risk factors control is necessary in individuals with an established vascular atherosclerosis.

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“…The common carotid artery was extracted and fixed. Immunohistochemistry was performed as described previously 12 with Egr-1 antibody.…”

Section: Adenoviral Vectors and Infectionmentioning

confidence: 99%

Constitutive Stimulation of Vascular Smooth Muscle Cells by Angiotensin II Derived From an Adenovirus Encoding a Furin-Cleavable Fusion Protein

Takayanagi

Bourne

Kimura

et al. 2012

American Journal of Hypertension

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A Disintegrin and Metalloprotease 17 Mediates Neointimal Hyperplasia in Vasculature

Cited by 29 publications

References 38 publications

Caveolin 1 is critical for abdominal aortic aneurysm formation induced by angiotensin II and inhibition of lysyl oxidase

Caveolin 1 is critical for abdominal aortic aneurysm formation induced by angiotensin II and inhibition of lysyl oxidase

A score including ADAM17 substrates correlates to recurring cardiovascular event in subjects with atherosclerosis

Constitutive Stimulation of Vascular Smooth Muscle Cells by Angiotensin II Derived From an Adenovirus Encoding a Furin-Cleavable Fusion Protein

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