Objective: Neutral endopeptidase (NEP, EC 3.4.24.11) metabolises endogenous vasoactive peptides that may protect against atherogenesis. Since NEP is found in the adventitia of arteries, we investigated the anti-atherogenic effects of chronic adventitial NEP inhibition.
Methods: Intimal hyperplasia of rabbit carotid arteries was induced by placement of soft, non-occlusive, peri-arterial silastic collars. NEP localisation was studied with autoradiography 7 and 14 days after collar placement. Vascular NEP was inhibited in vivo by local superfusion of one collared carotid artery with Candoxatrilat (50 pmol/h), for 7 days (n = 7). The contralateral collar was filled with saline vehicle. After 7 days, ring segments of collared and normal (proximal to the collar) arteries were obtained and in vitro functional measurements, immunohistochemical determination of the pro-atherogenic factor plasminogen activator inhibitor-1 (PAI-1), localization of macrophages and morphometric analyses were carried out.
Results: Vascular NEP radiolabelled substrate binding, mainly in the media, was increased by approximately 50% after 7 days (n = 5; p < 0.05) and by approximately 300% after 14 days of collar placement (n = 5; p < 0.05). Compared with normal artery segments from the same animal, vehicle-filled collared sections displayed significantly impaired vasorelaxation to acetylcholine (endothelium-independent vasodilatation was preserved), increased PAI-1 immunostaining, macrophage accumulation and intimal thickening. In Candoxatrilat-treated collared arteries, vasorelaxation to acetylcholine was improved, along with reductions in PAI-1 levels, macrophage numbers and intimal area (all p < 0.05).
Conclusion: Enhancing the activity of local, endogenous peptides by adventitial inhibition of vascular NEP may protect against early atherogenesis. This is of particular relevance to using adventitial therapies to prevent intimal hyperplasia leading to restenosis.
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http://dx.doi.org/10.1016/j.cardiores.2006.03.019 | DOI Listing |
J Mater Chem B
January 2025
Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Cardiovascular diseases (CVDs) are the foremost cause of mortality worldwide, with incidence and mortality rates persistently climbing despite extensive research efforts. Innovative therapeutic approaches are still needed to extend patients' lives and preserve their health. In the present study, novel supramolecular nanomedicine with both nitric oxide (NO) and antioxidant releasing ability was developed to enhance therapeutic efficacy against vascular injuries.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Department of Cardiology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
J Ethnopharmacol
December 2024
School of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, 300 Bachelor Road, Hanpu Science and Education Park, Yuelu District, 410208Changsha City, Hunan Province, China; Hunan Key Laboratory of Integrated Chinese and Western Medicine for Prevention and Treatment of Heart and Brain Diseases, 410208, Changsha, China. Electronic address:
Ethnopharmacological Relevance: Astragali Radix-Angelicae Sinensis Radix is an important traditional Chinese medicine used for the treatment of cardiovascular diseases. Our previous studies have shown that Astragali Radix-Angelicae Sinensis Radix can inhibit vascular intimal hyperplasia and improve the blood vessel wall's ECM deposition, among which six main active components can be absorbed into the blood, suggesting that these components may be the main pharmacodynamic substances of Astragali Radix-Angelicae Sinensis Radix against vascular intimal hyperplasia.
Aim Of The Study: A mouse model of atherosclerosis was used to study the relationship between the anti-intimal hyperplasia effect of Astragali Radix-Angelicae Sinensis Radix and the inhibition of VAF activation and ECM synthesis.
ACS Nano
December 2024
Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Synthetic vascular grafts are promising conduits for small caliber arteries. However, due to restenosis caused by intimal hyperplasia, they cannot keep long patency in vivo. In this work, through single cell RNA sequencing, we found that thrombospondin-1 (THBS1) was highly expressed in the regenerated smooth muscle cells (SMCs) in electrospun polycaprolactone (PCL) vascular grafts.
View Article and Find Full Text PDFVascular
December 2024
Department of Vascular Surgery, Xiamen Branch of Zhongshan Hospital, Fudan University, Xiamen, China.
Background: Endovascular recanalization with venous stenting is the preferred treatment for iliofemoral venous obstruction. We reviewed our institutional experience and mid-term outcomes with endovascular therapy for iliofemoral venous obstruction using the Venovo Self-expanding Venous Stent (BARD Peripheral Vascular, Inc., Tempe, AZ, USA).
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