Background and Purpose
Abdominal aortic aneurysm (AAA) is a degenerative disease affecting human health, but there are no safe and effective medications for AAA therapy. Cycloastragenol (CAG), derived from Astragali Radix, has various pharmacological effects. However, whether CAG can protect against AAA remains elusive. In this study, we investigated whether CAG has an inhibitory effect on AAA and its related mechanism.
Experimental Approach
The AAA mouse model was induced by incubating the abdominal aorta with elastase. CAG was administered by gavage at different doses beginning on the same day or 14 days after inducing AAA to explore its preventive or therapeutic effects respectively. The preventive effects of CAG on AAA were verified in another AAA mouse model induced by angiotensin II in ApoE−/− mouse. In vitro experiments were implemented on rat vascular smooth muscle cells (VSMCs) stimulated by TNF‐α.
Key Results
Compared to the control AAA model group, CAG (125 mg·kg−1 body weight day−1) reduced the incidence of AAA, the dilatation of aorta and elastin degradation in media in both mouse models of AAA. CAG suppressed the inflammation, oxidation, phenotype switch and apoptosis in TNF‐α‐stimulated VSMCs, ameliorated the expression and activity of MMPs and decreased the activation of the ERK/JNK signalling pathway. CAG also inhibited the degradation of elastin in TNF‐α‐stimulated VSMCs.
Conclusion and Implications
CAG presents protective effects against AAA through down‐regulation of the MAPK signalling pathways and thus attenuates inflammation, oxidation, VSMC phenotype switch and apoptosis and the expression of MMPs as well as increasing elastin biosynthesis.
Dendrimers, as a type of artificially synthesized polymers, have been increasingly attracting attention in many research fields, including the material and medical sciences, due to their unique characteristics that include their highly branched and well-defined molecular architecture, multivalency and tunable chemical compositions. These advantages make dendrimers potential carriers for the delivery of therapeutic and diagnostic agents. Herein, we review the recent advances in dendrimer research for the prevention and treatment of cardiovascular diseases, with special focus on their applications as carriers for drug and gene delivery, as contrast agents, and as potential new drugs.
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