Not just correlative: a new pathway defines how an ALDH2 SNP contributes to atherosclerosis

Gibb, Andrew; Elrod, John W.

doi:10.1172/jci125433

Cited by 8 publications

(6 citation statements)

References 12 publications

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“…Gibb et al. found that the ALDH2 rs671 mutant could repress the transcription of a lysosomal H+ pump subunit in nucleus, which is crucial for lipid degradation and foam cell formation ( 82 ). Besides, Zhong et al.…”

Section: Discussionmentioning

confidence: 99%

The ALDH2 gene rs671 polymorphism is associated with cardiometabolic risk factors in East Asian population: an updated meta-analysis

Liu,

Peng,

Zhang

et al. 2024

Front. Endocrinol.

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IntroductionAcetaldehyde dehydrogenase 2 (ALDH2) had reported as a prominent role in the development of cardiometabolic diseases among Asians. Our study aims to investigate the relationship between ALDH2 polymorphism and cardiometabolic risk factors in East Asian population.MethodWe searched databases of PubMed, Web of Science, and Embase updated to Oct 30th, 2023. We extracted data of BMI, Hypertension, SBP, DBP, T2DM, FBG, PPG, HbA1c, TG, TC, LDL-C and HDL-C.ResultIn total, 46 studies were finally included in our meta-analysis, containing, 54068 GG and, 36820 GA/AA participants. All outcomes related to blood pressure revealed significant results (hypertension OR=0.83 [0.80, 0.86]; SBP MD=-1.48 [-1.82, -1.14]; DBP MD=-1.09 [-1.58, -0.61]). FBG showed a significant difference (MD=-0.10 [-0.13, -0.07]), and the lipid resulted significantly in some outcomes (TG MD=-0.07 [-0.09, -0.04]; LDL-C MD=-0.04 [-0.05, -0.02]). As for subgroups analysis, we found that in populations without severe cardiac-cerebral vascular diseases (CCVDs), GG demonstrated a significantly higher incidence of T2DM (T2DM OR=0.88 [0.79, 0.97]), while the trend was totally opposite in population with severe CCVDs (T2DM OR=1.29 [1.00, 1.66]) with significant subgroup differences.ConclusionOur updated meta-analysis demonstrated that ALDH2 rs671 GG populations had significantly higher levels of BMI, blood pressure, FBG, TG, LDL-C and higher risk of hypertension than GA/AA populations. Besides, to the best of our knowledge, we first report GG had a higher risk of T2DM in population without severe CCVDs, and GA/AA had a higher risk of T2DM in population with severe CCVDs.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023389242.

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Section: Discussionmentioning

confidence: 99%

The ALDH2 gene rs671 polymorphism is associated with cardiometabolic risk factors in East Asian population: an updated meta-analysis

Liu,

Peng,

Zhang

et al. 2024

Front. Endocrinol.

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“…Mechanistically, this point mutation impaired the efferocytotic activity of macrophages in mice. 126,127 Dysregulated efferocytosis leads to the accumulation of apoptotic macrophages, which causes further necrotic core expansion and fuels the pro-inflammatory microenvironment. 128 Utilization of biomolecules from the engulfed cargo from initial efferocytic events affects efficacy of subsequent rounds.…”

Section: Efferocytosis In Cvdmentioning

confidence: 99%

“…The ALDH2 rs671 single‐point mutation is a risk factor associated with poor CVD outcomes. Mechanistically, this point mutation impaired the efferocytotic activity of macrophages in mice 126,127 . Dysregulated efferocytosis leads to the accumulation of apoptotic macrophages, which causes further necrotic core expansion and fuels the pro‐inflammatory microenvironment 128 .…”

Section: Macrophage Efferocytosis In Cvdmentioning

confidence: 99%

Macrophage mediators and mechanisms in cardiovascular disease

Schelemei,

Wagner,

Picard

et al. 2024

The FASEB Journal

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Macrophages are major players in myocardial infarction (MI) and atherosclerosis, two major cardiovascular diseases (CVD). Atherosclerosis is caused by the buildup of cholesterol‐rich lipoproteins in blood vessels, causing inflammation, vascular injury, and plaque formation. Plaque rupture or erosion can cause thrombus formation resulting in inadequate blood flow to the heart muscle and MI. Inflammation, particularly driven by macrophages, plays a central role in both atherosclerosis and MI. Recent integrative approaches of single‐cell analysis‐based classifications in both murine and human atherosclerosis as well as experimental MI showed overlap in origin, diversity, and function of macrophages in the aorta and the heart. We here discuss differences and communalities between macrophages in the heart and aorta at steady state and in atherosclerosis or upon MI. We focus on markers, mediators, and functional states of macrophage subpopulations. Recent trials testing anti‐inflammatory agents show a major benefit in reducing the inflammatory burden of CVD patients, but highlight a necessity for a broader understanding of immune cell ontogeny and heterogeneity in CVD. The novel insights into macrophage biology in CVD represent exciting opportunities for the development of novel treatment strategies against CVD.

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“…However, the underlying molecular mechanisms linking ALDHs to cholesterol metabolism await further investigation. We identified a potentially novel role of ALDH2 in macrophage foam cell formation through interactions with LDL receptor (LDLR) and AMPK (29), linking ALDH2 SNP with increased risks of CVD beyond alcohol consumption (32). Further study showed that hepatic ALDH2 regulates the protein stability of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of cholesterol de novo synthesis and target of statins; ALDH2 rs671 variant stabilizes HMGCR and promotes cholesterol synthesis, which leads to higher levels of total cholesterol in mice and humans (29,33).…”

Section: Introductionmentioning

confidence: 99%

Aldehyde dehydrogenase 2 and PARP1 interaction modulates hepatic HDL biogenesis by LXRα-mediated ABCA1 expression

Li¹,

Zhong²,

Li³

et al. 2022

JCI Insight

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Not just correlative: a new pathway defines how an ALDH2 SNP contributes to atherosclerosis

Cited by 8 publications

References 12 publications

The ALDH2 gene rs671 polymorphism is associated with cardiometabolic risk factors in East Asian population: an updated meta-analysis

The ALDH2 gene rs671 polymorphism is associated with cardiometabolic risk factors in East Asian population: an updated meta-analysis

Macrophage mediators and mechanisms in cardiovascular disease

Aldehyde dehydrogenase 2 and PARP1 interaction modulates hepatic HDL biogenesis by LXRα-mediated ABCA1 expression

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