Cardiotonic Pills Plus Recombinant Human Prourokinase Ameliorates Atherosclerotic Lesions in LDLR–/– Mice

Abstract

AimThis study was to explore the protective effects of cardiotonic pills (CP) or/and recombinant human prourokinase (proUK)on the atherosclerosis and the potential underlying mechanism.Methods and ResultsAtherosclerosis was induced in LDLR–/– mice by high fat diet contained 20% lard and 0.5% cholesterol. Daily oral administration of CP (130 mg/kg) or/and intravenous injection of proUK (2.5 mg/kg, twice a week) began at 8 weeks after feeding with high fat diet and continued for 4 weeks. CP alone treatment markedly decreased plasma triglyceride, but did not ameliorate atherosclerosis plaque. No effect was observed for proUK alone on any endpoints tested. CP plus proUK induced a significantly reduction in the atherosclerotic lesions, along with decreased levels of total cholesterol, triglyceride in the plasma. CP plus proUK inhibited the elevated hepatic total cholesterol and triglyceride in high fat diet-fed LDLR–/– mice, up-regulating the expressions of ATP-binding cassette gene 5 and 8, and adipose triglyceride lipase. In the aorta, CP plus proUK inhibited the expression of scavenger receptor A and CD36 in LDLR–/– mice. In addition, we observed that systemic inflammation was inhibited, manifested downregulation of plasma macrophage inflammatory protein-1α and intercellular cell adhesion molecule-1.ConclusionCP plus proUK effectively attenuated atherosclerosis plaque in LDLR–/– mice, which is associated with normalizing the lipid metabolism in the liver and aorta, reducing phagocytosis of receptor-mediated modified-LDL uptake and inhibiting systemic inflammation.

S-nitrosylation-mediated coupling of G-protein alpha-2 with CXCR5 induces Hippo/YAP-dependent diabetes-accelerated atherosclerosis

“…3b, c ). These results were in accordance with what observed by Deng, J. N, et al 38 AAV endo -GNAI2-C66A enhanced plaque stability compared to AAV endo -GFP and AAV endo -GNAI2-WT in STZ + HFD-treated LDLr −/− mice, as evidenced by smaller necrotic cores, thicker fibrous cap (Supplementary Fig. 3a, b ), increased collagen and smooth muscle cells content and reduced macrophage infiltration and lipid deposition (Fig.…”

Editorial: Traditional Chinese Medicine: Organ Vascular Injury - Volume II

“…Gu et al from the team of professors Jing-Yan Han and Zhi-Zhong Ma demonstrated that YangXue Qing Nao Wan and Silibinin Capsules could improve cognitive impairment of aged LDLR (+/-) golden Syrian hamsters, which was associated with attenuated albumin leakage from middle cerebral artery and neuronal damage in hippocampus, concomitant with an increase in cerebral blood flow, a decrease of perivascular edema and an up-regulated expression of claudin-5, occludin and ZO-1 (Gu et al, 2018). Deng et al from the team of professor Jing-Yan Han also demonstrated that combination of Cardiotonic Pills, a compound Chinese medicine for coronary heart disease and angina pectoris, and recombinant human prourokinase, a thrombolytic drug, effectively attenuated atherosclerosis plaque in LDLR −/− mice plus high fat diet, which is associated with normalizing the lipid metabolism in the liver and aorta, reducing phagocytosis of receptor-mediated modified-LDL uptake and inhibiting systemic inflammation (Deng et al, 2019).…”