European journal of medical research · 2025
Association of lipoprotein(a) and LPA gene with calcific aortic valve disease.
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Yu Xinyi, Fu Zean, Yu Minghuan, Shi Yibo
Аннотация
OBJECTIVE: To investigate the association between Lp(a) levels and calcific aortic valve disease (CAVD) and the potential molecular mechanism underlying the effect of LPA gene expression on aortic valve calcification (AVC).
METHODS: Case-control and cohort studies on the association between Lp(a) and CAVD were searched in the meta-analysis. Meta-analysis was performed using RevMan and Stata. AVC-related gene microarray data were obtained from the GEO database. The Gene Set Variation Analysis (GSVA) algorithm was used to synthetically score each gene set and analyze differences in pathways in the LPA gene high- and low-expression groups. The expression of endothelial markers, interstitial markers and osteogenic markers after Lp(a) intervention in human aortic valve endothelial cells (AVEC) was detected by Western blot.
RESULTS: The risk of CAVD was increased 1.44-fold (95% CI 1.25-1.67, P < 0.05) when Lp(a) concentrations were > 30 mg/dL and 1.95-fold (95% CI 1.93-1.97, P < 0.05) when Lp(a) concentrations were > 50 mg/dL. GSVA results showed that high expression of the LPA gene was associated with TGF-β signaling, oxidative phosphorylation, and reactive oxygen species pathway. Western-blot results showed that after Lp(a) was co-cultured with AVEC for 72 h, the expression of endothelial markers decreased, while the expression of interstitial markers and osteogenic markers increased.
CONCLUSION: Elevated Lp(a) concentration is a risk factor for CAVD. High expression of the LPA gene (or high concentration of Lp(a)) may cause EndoMT of AVEC by disrupting pathways, such as TGF-β signaling, resulting in CAVD.
METHODS: Case-control and cohort studies on the association between Lp(a) and CAVD were searched in the meta-analysis. Meta-analysis was performed using RevMan and Stata. AVC-related gene microarray data were obtained from the GEO database. The Gene Set Variation Analysis (GSVA) algorithm was used to synthetically score each gene set and analyze differences in pathways in the LPA gene high- and low-expression groups. The expression of endothelial markers, interstitial markers and osteogenic markers after Lp(a) intervention in human aortic valve endothelial cells (AVEC) was detected by Western blot.
RESULTS: The risk of CAVD was increased 1.44-fold (95% CI 1.25-1.67, P < 0.05) when Lp(a) concentrations were > 30 mg/dL and 1.95-fold (95% CI 1.93-1.97, P < 0.05) when Lp(a) concentrations were > 50 mg/dL. GSVA results showed that high expression of the LPA gene was associated with TGF-β signaling, oxidative phosphorylation, and reactive oxygen species pathway. Western-blot results showed that after Lp(a) was co-cultured with AVEC for 72 h, the expression of endothelial markers decreased, while the expression of interstitial markers and osteogenic markers increased.
CONCLUSION: Elevated Lp(a) concentration is a risk factor for CAVD. High expression of the LPA gene (or high concentration of Lp(a)) may cause EndoMT of AVEC by disrupting pathways, such as TGF-β signaling, resulting in CAVD.