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.
Highlights
Atherosclerosis (AS) is a chronic disease of the arterial wall which is the leading cause of disability and death around the world (Castelli et al, 1986; Pant et al, 2014)
cardiotonic pill (CP) Plus proUK Slows Down the Progression of Atherosclerosis Plaque in LDLR−/− Mice
Figure 1A7 revealed that treatment with 6 mg/kg atorvastatin plus 15 mg/kg aspirin for 4 weeks significantly inhibited the development of high fat-diet induced atherosclerotic plaques in LDLR−/− mice
Summary
Atherosclerosis (AS) is a chronic disease of the arterial wall which is the leading cause of disability and death around the world (Castelli et al, 1986; Pant et al, 2014). Hyperlipidemia, system inflammation and hypertensionare thought to be the major risk factors in the formation and development of AS (Zhu et al, 2018). Plasma low-density lipoprotein (LDL) levels have a positive association with the development of AS. AS is initiated by endothelial dysfunction predominantly due to the accumulation of plasma LDL (Alonso et al, 2014). Endothelial cell dysfunction leads to the infiltration of LDL particles and their subsequent oxidation to oxidized-LDL (ox-LDL). Macrophages differentiated from circulating monocyte take up ox-LDL via scavenger receptor A(SR-A) and CD36 to form foam cell (Lusis, 2000; Zhu et al, 2018)
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