Acetaldehyde dehydrogenase 2 interactions with LDLR and AMPK regulate foam cell formation

Zhong, Shanshan; Li, Luxiao; Zhang, Yulei; Zhang, Lili; Lu, Jianhong; Guo, Shuyuan; Liang, Ningning; Ge, Jing; Zhu, Mingyang; Tao, Yongzhen; Wu, Yuncheng; Yin, Huiyong

doi:10.1172/jci122064

Cited by 73 publications

(68 citation statements)

References 45 publications

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“…In summary, the current study by Zhong et al (5) makes an important mechanistic link regarding the increased prevalence of atherosclerosis in individuals with the ALDH2 rs671 SNP. While the complete underlying mechanisms remain to be elucidated, these findings provide the framework to further delineate the involvement of ALDH2 in not only atherosclerosis, but numerous other disease states of clinical significance.…”

Section: Conclusion and Clinical Implicationsmentioning

confidence: 71%

“…In this issue, Zhong et al provide important mechanistic evidence to address the role of ALDH2 rs671 in CVD (5). The authors employed mouse genetics and deleted Aldh2 in the Ldlr knockout background (Ldlr -/-), a commonly employed experimental model of atherosclerosis, and demonstrated that loss of ALDH2 reduced plaque burden and foam cell formation (fat laden macrophages that contribute to plaque generation and growth).…”

Section: Aldh2 and Atherosclerosis Developmentmentioning

confidence: 99%

“…While the study by Zhong et al provides causative evidence linking ALDH2 to atherosclerosis (5), the exact role of ALDH2 in disease progression remains to be elucidated. There are several questions that have been brought to light by the current study and require further investigation to provide a more holistic view.…”

Section: Conclusion and Clinical Implicationsmentioning

confidence: 99%

“…An ALDH2 SNP contributes to atherosclerosis. In this issue of the JCI, Zhong et al(5) identify a pathway that reveals how the ALDH2 rs671 SNP promotes atherosclerosis. (A) The low-density lipoprotein receptor (LDLR) physically interacts with aldehyde dehydrogenase 2 (ALDH2) and 5′ AMP-activated protein kinase (AMPK) to prevent AMPK-mediated phosphorylation and subsequent nuclear translocation of ALDH2.…”

mentioning

confidence: 99%

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

Gibb¹,

Elrod²

2018

Journal of Clinical Investigation

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Section: Conclusion and Clinical Implicationsmentioning

confidence: 71%

Section: Aldh2 and Atherosclerosis Developmentmentioning

confidence: 99%

Section: Conclusion and Clinical Implicationsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

Gibb¹,

Elrod²

2018

Journal of Clinical Investigation

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“…3C). Aldh2 encoded by Aldh2, mostly known for its role in alcohol detoxification, was recently reported to play a role in repression of ATP6V0E2, which is critical for proper lysosomal function, autophagy, and degradation of oxidized LDL 35 (Fig. 3C).…”

Section: Monocyte Differentiation Into Gut Segment-specific Macrophagesmentioning

confidence: 99%

Defining Monocyte Differentiation into Colonic and Ileal Macrophages

Gross-Vered

Shemer

Bernshtein

et al. 2019

Preprint

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Monocytes are circulating short-lived macrophage precursors that are recruited on demand from the blood to sites of inflammation and challenge. In steady state, classical monocytes give rise to vasculature-resident cells that patrol the luminal side of the endothelium. In addition, classical monocytes feed macrophage compartments of selected organs, including barrier tissues, such as the skin and intestine, as well as the heart. Monocyte differentiation under conditions of inflammation has been studied in considerable detail. In contrast, monocyte differentiation under non-inflammatory conditions remains less well understood.Here we took advantage of a combination of cell ablation and precursor engraftment to investigate the generation of gut macrophages from monocytes. Collectively, we identify factors associated with the gradual adaptation of monocytes to tissue residency. Moreover, comparison of monocyte differentiation into the colon and ileum-resident macrophages revealed the graduated acquisition of gut segment-specific gene expression signatures.

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Early Progression of Abdominal Aortic Aneurysm is Decelerated by Improved Endothelial Barrier Function via ALDH2‐LIN28B‐ELK3 Signaling

Yang,

Cui,

Wang

et al. 2023

Advanced Science

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The involvement of endothelial barrier function in abdominal aortic aneurysm (AAA) and its upstream regulators remains unknown. Single‐cell RNA sequencing shows that disrupted endothelial focal junction is an early (3 days) and persistent (28 days) event during Angiotensin II (Ang II)‐induced AAA progression. Consistently, mRNA sequencing on human aortic dissection tissues confirmed downregulated expression of endothelial barrier‐related genes. Aldehyde dehydrogenase 2 (ALDH2), a negative regulator of AAA, is found to be upregulated in the intimal media of AAA samples, leading to testing its role in early‐stage AAA. ALDH2 knockdown/knockout specifically in endothelial cells (ECs) significantly increases expression of EC barrier markers related to focal adhesion and tight junction, restores endothelial barrier integrity, and suppresses early aortic dilation of AAA (7 and 14 days post‐Ang II). Mechanically, ELK3 acts as an ALDH2 downstream regulator for endothelial barrier function preservation. At the molecular level, ALDH2 directly binds to LIN28B, a regulator of ELK3 mRNA stability, hindering LIN28B binding to ELK3 mRNA, thereby depressing ELK3 expression and impairing endothelial barrier function. Therefore, preserving vascular endothelial barrier integrity via ALDH2‐specific knockdown in ECs holds therapeutic potential in the early management of AAAs.

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Acetaldehyde dehydrogenase 2 interactions with LDLR and AMPK regulate foam cell formation

Cited by 73 publications

References 45 publications

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

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

Defining Monocyte Differentiation into Colonic and Ileal Macrophages

Early Progression of Abdominal Aortic Aneurysm is Decelerated by Improved Endothelial Barrier Function via ALDH2‐LIN28B‐ELK3 Signaling

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