ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway

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	ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway
	Chen, F; Chen, YT; Ke, QW; Wang, YX; Gong, Z; Chen, XJ; Cai, YJ; Li, SN; Sun, YH; Peng, XP; Ji, Y; Zhang, TZ; Wu, WX; Cui, LL; Wang, Y
	2023
发表期刊	JOURNAL OF TRANSLATIONAL MEDICINE
卷号	21 期号:1
摘要	BackgroundRecent numerous epidemiology and clinical association studies reported that ApoE polymorphism might be associated with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes.MethodsA meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and the SARS-CoV-2 primary receptor ACE2, ApoE and spike protein. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression.ResultsApoE gene polymorphism (epsilon 4 carrier genotypes VS non-epsilon 4 carrier genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI 1.18-1.76) and progression (P < 0.00001, OR = 1.85, 95% CI 1.50-2.28) of COVID-19. ApoE interacts with both ACE2 and the spike protein but did not show isoform-dependent binding effects. ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7.ConclusionsApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Instead, ApoE4 downregulates ACE2 protein expression and subsequently the dysregulation of renin-angiotensin system (RAS) may provide explanation by which ApoE4 exacerbates COVID-19 disease.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14083
专题	其他
推荐引用方式 GB/T 7714	Chen, F,Chen, YT,Ke, QW,et al. ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway[J]. JOURNAL OF TRANSLATIONAL MEDICINE,2023,21(1).
APA	Chen, F.,Chen, YT.,Ke, QW.,Wang, YX.,Gong, Z.,...&Wang, Y.(2023).ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway.JOURNAL OF TRANSLATIONAL MEDICINE,21(1).
MLA	Chen, F,et al."ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway".JOURNAL OF TRANSLATIONAL MEDICINE 21.1(2023).

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