CRD affects post-infarction cardiac remodeling through influencing myocardial lipid metabolism:a mechanistic study

Hu Ruijie; Jiao Liying; Tan Wuping; Jiang Hong

doi:10.3969/j.issn.1009-0126.2024.04.019

Abstract：Objective To investigate whether circadian rhythm disorders(CRD)exacerbate cardiac remodeling after MI and potential lipid metabolism-related mechanisms.Methods Eighteen healthy SPF-grade male SD rats were randomly divided into sham-operation(sham)group,MI group and CRD(MI+Dis)group,with 6 rats in each group.After 14 d of acclimatization,the MI and MI+Dis groups were established as MI models,and the MI+Dis group received 24 h continu-ous light for 7 d to establish a CRD model.Echocardiography was used to assess cardiac function,HE staining to observe MI-induced myocardial injury,Masson staining to measure myocardial col-lagen fiber expression,immunofluorescence assay to detect myocardial fibrosis marker α-SMA ex-pression,RT-PCR to determine the mRNA levels of carnitine palmitoyltransferase 1β(CPT-1β),peroxisome proliferator-activated receptor α(PPARα),Collagen type Ⅰ and Collagen type Ⅲ,and biochemical tests to measure the serum levels of triglyceride(TG)and total cholesterol(TC).Re-sults The MI group had significantly larger LVESD and LVEDD and increased expression of myocardial α-SMA,Collagen Ⅰ,and Collagen Ⅲ,and reduced LVEF and LVFS when compared with the sham group(P＜0.05,P＜0.01).Obviously larger LVESD and LVEDD(8.27±0.66 mm vs 5.82±0.54 mm,10.13±0.71 mm vs 7.97±0.55 mm,P＜0.05),increased expression levels of myocardial α-SMA,Collagen Ⅰ and Collagen Ⅲ,and elevated serum TG and TC levels(P＜0.05,P＜0.01),and smaller LVEF and LVFS,and decreased myocardial CPT-1β,and PPARα(P＜0.05)were observed in the MI+Dis group than the MI group.Conclusion CRD may lead to lipid accumulation and aggravate cardiac remodeling after MI by inhibiting myocardial fatty acid β oxi-dation and disturbing cardiac energy metabolism homeostasis.