Endothelial-Specific Expression of CIDEC Improves High-Fat Diet–Induced Vascular and Metabolic Dysfunction

Balakrishnan, Bijinu; Gupta, Abhishek; Basri, Rabia; Sharma, Vishva Mitra; Slayton, Mark; Gentner, Kailey; Becker, Chloe C.; Karki, Shakun; Muturi, Harrison T.; Najjar, Sonia M.; Loria, Analia S.; Gokce, Noyan; Puri, Vishwajeet

doi:10.2337/db22-0294

Cited by 6 publications

(4 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, insulin resistance can induce an imbalance in lipoproteins profle alterations that contributes to the development of dyslipidemia and the lipid triad ( 41 ). The abnormal association between insulin resistance and endothelial signal conduction disorder leads to inflammation, which further disrupts the balance between endothelial vasodilator and vasoconstrictor mechanisms, and leads to the formation of atherosclerotic plaque ( 40 , 42 ). New therapies focused on decreasing insulin resistance may be investigated as a potential future therapeutic target for mitigating both CVD and atherosclerotic plaque generation.…”

Section: Discussionmentioning

confidence: 99%

Age at diagnosis, diabetes duration and the risk of cardiovascular disease in patients with diabetes mellitus: a cross-sectional study

Yao

Zhang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundThe purpose of the study was to evaluate characteristics and risk of cardiovascular disease (CVD) according to age at diagnosis and disease duration among adults with diabetes mellitus (DM).MethodsThe association between age at diagnosis, diabetes duration and CVD were examined in 1,765 patients with DM. High risk of estimated ten-year atherosclerotic cardiovascular disease (ASCVD) was performed by the Prediction for ASCVD Risk in China (China-PAR) project. Data were compared with analysis of variance and χ2 test, respectively. Multiple logistic regression was used to determine the risk factors of CVD.ResultsThe mean age at diagnosis (± standard deviation) was 52.91 ± 10.25 years and diabetes duration was 8.06 ± 5.66 years. Subjects were divided into early-onset DM group (≤43 years), late-onset DM group (44 to 59 years), elderly-onset DM group (≥60 years) according to age at diagnosis. Diabetes duration was classified by 5 years. Both early-onset and longest diabetes duration (>15 years) had prominent hyperglycaemia. Diabetes duration was associated with the risk of ischemic stroke (odds ratio (OR), 1.091) and coronary artery disease (OR, 1.080). Early-onset group (OR, 2.323), and late-onset group (OR, 5.199), and hypertension (OR, 2.729) were associated with the risk of ischemic stroke. Late-onset group (OR, 5.001), disease duration (OR, 1.080), and hypertension (OR, 2.015) and hyperlipidemia (OR, 1.527) might increase the risk of coronary artery disease. Aged over 65 (OR, 10.192), central obesity (OR, 1.992), hypertension (OR, 18.816), cardiovascular drugs (OR, 5.184), antihypertensive drugs (OR, 2.780), and participants with disease duration >15 years (OR, 1.976) were associated with the high risk of estimated ten-year ASCVD in participants with DM.ConclusionAge at diagnosis, diabetes duration, hypertension and hyperlipidemia were independent risks of CVD. Longest (>15 years) diabetes duration increased the high risk of ten-year ASCVD prediction among Chinese patients with DM. It’s urgent to emphasize the importance of age at diagnosis and diabetes duration to improve primary complication of diabetes.

show abstract

Section: Discussionmentioning

confidence: 99%

Age at diagnosis, diabetes duration and the risk of cardiovascular disease in patients with diabetes mellitus: a cross-sectional study

Yao

Zhang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…Interestingly, an emerging role for CIDEC as modulator of vascular function and VEGF signaling has been recently proposed [ 49 , 50 ]. Although in our study, CIDEC mRNA was below detection limit in human retina, RPE and choroid, CIDEC expression in vascular endothelial cells has been observed in other human tissue such as subcutaneous or visceral fat [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although in our study, CIDEC mRNA was below detection limit in human retina, RPE and choroid, CIDEC expression in vascular endothelial cells has been observed in other human tissue such as subcutaneous or visceral fat [ 49 ]. Using a mouse expressing human CIDEC in vascular endothelial cells, it was shown that CIDEC enhance vascular remodeling, angiogenesis and stabilize VEGF signaling [ 50 ]. Since the CIDEC rare variants were identified in neovascular AMD patients, it is unlikely that they critically affect this potential pro-angiogenic role of CIDEC.…”

Section: Discussionmentioning

confidence: 99%

Rare CIDEC coding variants enriched in age-related macular degeneration patients with small low-luminance deficit cause lipid droplet and fat storage defects

Kim¹,

Stockwell²,

Qin³

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

Background The basis of Age-related macular degeneration (AMD) genetic risk has been well documented; however, few studies have looked at genetic biomarkers of disease progression or treatment response within advanced AMD patients. Here we report the first genome-wide analysis of genetic determinants of low-luminance vision deficit (LLD), which is seen as predictive of visual acuity loss and anti-VEGF treatment response in neovascular AMD patients. Methods AMD patients were separated into small- and large-LLD groups for comparison and whole genome sequencing was performed. Genetic determinants of LLD were assessed by common and rare variant genetic analysis. Follow-up functional analysis of rare coding variants identified by the burden test was then performed in vitro. Results We identified four coding variants in the CIDEC gene. These rare variants were only present in patients with a small LLD, which has been previously shown to indicate better prognosis and better anti-VEGF treatment response. Our in vitro functional characterization of these CIDEC alleles revealed that all decrease the binding affinity between CIDEC and the lipid droplet fusion effectors PLIN1, RAB8A and AS160. The rare CIDEC alleles all cause a hypomorphic defect in lipid droplet fusion and enlargement, resulting in a decreased fat storage capability in adipocytes. Conclusions As we did not detect CIDEC expression in the ocular tissue affected by AMD, our results suggest that the CIDEC variants do not play a direct role in the eye and influence low-luminance vision deficit via an indirect and systemic effect related to fat storage capacity.

show abstract

“…The activation of the ADRB2/PKA signaling pathway promotes lipid synthesis in human lid gland epithelial cells and also provides a potential mechanism and therapeutic target for dry eye disease [ 37 ]. Previous reports have indicated that cell-death-inducing DNA fragmentation factor-α-like effector C ( CIDEC ) is positively relates to insulin sensitivity, whereas the expression of endothelial-specific CIDEC improves vascular and metabolic dysfunction induced by a high-fat diet [ 38 ]. Bi-allelic SLC4A2 loss-of-function mutations in mice and cattle lead to osteopetrosis with osteoclast deficiency [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Selection Signal of the Tibetan Black Chicken Genome Based on Whole-Genome Sequencing

Feng,

Zhu,

Shi

et al. 2023

Genes

View full text Add to dashboard Cite

Background: The Tibetan chicken has adapted well to high altitudes genetically after its long-term habitation in the plateau. In this study, we analyzed the selection signal of Tibetan black chickens (TBCs) and discovered genes associated with the characteristics of germplasm. Methods: Whole-genome sequencing (WGS) was used to identify the single-nucleotide polymorphism (SNP) markers and genetic structures in the genome of Tibetan black chickens. Further, we performed a comparative population genomics analysis between the genomic data obtained in this present study and the genomic data for five wild red jungle fowls (RJFs) accessed from the NCBI database (GenBank accession number PRJNA241474). Thereafter, the Fst and Pi selections were used to identify genes under positive selection in the Tibetan black chicken genome. Results: A total of 9,490,690 SNPs were identified in the Tibetan black chickens. In addition, the results from the gene ontology (GO) analysis showed that 732 genes of TBCs were enriched in a total of 210 GO terms with specific molecular functions such as regulation of cellular catabolic process, the MAPK signaling pathway, regulation of ion transport, growth, morphogenesis and lung alveolus development which may provide a better mechanism to facilitate oxygen transport and utilization in TBCs. Moreover, the results from the KEGG analysis showed that 732 genes of the TBCs were significantly enriched in the calcium signaling pathway, circadian entrainment (ADCY1, GNG7 and PER3), oxytocin signaling pathway and pathways of multiple neurodegeneration diseases. In addition, the CD86 antigen (CD86) was identified as a gene associated with the immune response in chickens. It was also revealed that genes such as TRIT1, HPCAL4, NT5C1A and HEYL were discovered under selection in Tibetan black chickens on chromosome 23. These genes may be related to the local adaptive characteristics of Tibetan black chickens, for instance, NT5C1A and HEYL may be involved in the high-altitude adaption of oxygen delivery in Tibetan black chickens. Conclusions: In summary, we found that selection mainly affects the disease resistance and cold acclimatization of Tibetan black chickens. Hence, these results may provide important genetic information for the evolution and breeding of Tibetan black chickens.

show abstract

Endothelial-Specific Expression of CIDEC Improves High-Fat Diet–Induced Vascular and Metabolic Dysfunction

Cited by 6 publications

References 53 publications

Age at diagnosis, diabetes duration and the risk of cardiovascular disease in patients with diabetes mellitus: a cross-sectional study

Age at diagnosis, diabetes duration and the risk of cardiovascular disease in patients with diabetes mellitus: a cross-sectional study

Rare CIDEC coding variants enriched in age-related macular degeneration patients with small low-luminance deficit cause lipid droplet and fat storage defects

Analysis of the Selection Signal of the Tibetan Black Chicken Genome Based on Whole-Genome Sequencing

Contact Info

Product

Resources

About