New insights on the cardiovascular effects of IGF-1

Mačvanin, Mirjana; Gluvić, Zoran; Radovanović, Jelena; Essack, Magbubah; Gao, Xin; Isenović, Esma R.

doi:10.3389/fendo.2023.1142644

Cited by 24 publications

(19 citation statements)

References 223 publications

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“…Additionally, AF can be an intractable dysrhythmia, so identifying the gene–environment interactions underlying this disease may uncover novel therapeutic strategies to better reverse the underlying pathogenesis. In particular, in these context, drugs and bioactive molecules, exerts their beneficial effects via epigenetic regulations 67–69 . Our findings further underscore the exciting potential of novel ‘epidrugs’ targeting the methylation‐sensitive underpinnings of AF.…”

Section: Discussionmentioning

confidence: 56%

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CDK5R1, GSE1, HSPG2 and WDFY3 as indirect epigenetic‐sensitive genes in atrial fibrillation

Infante,

Pepin,

Ruocco

et al. 2023

Eur J Clin Investigation

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BackgroundAlthough mounting evidence supports that aberrant DNA methylation occurs in the hearts of patients with atrial fibrillation (AF), noninvasive epigenetic characterization of AF has not yet been defined.MethodsWe investigated DNA methylome changes in peripheral blood CD4+ T cells isolated from 10 patients with AF relative to 11 healthy subjects (HS) who were enrolled in the DIANA clinical trial (NCT04371809) via reduced‐representation bisulfite sequencing (RRBS).ResultsAn atrial‐specific PPI network revealed 18 hub differentially methylated genes (DMGs), wherein ROC curve analysis revealed reasonable diagnostic performance of DNA methylation levels found within CDK5R1 (AUC = 0.76; p = 0.049), HSPG2 (AUC = 0.77; p = 0.038), WDFY3 (AUC = 0.78; p = 0.029), USP49 (AUC = 0.76; p = 0.049), GSE1 (AUC = 0.76; p = 0.049), AIFM1 (AUC = 0.76; p = 0.041), CDK5RAP2 (AUC = 0.81; p = 0.017), COL4A1 (AUC = 0.86; p < 0.001), SEPT8 (AUC = 0.90; p < 0.001), PFDN1 (AUC = 0.90; p < 0.01) and ACOT7 (AUC = 0.78; p = 0.032). Transcriptional profiling of the hub DMGs provided a significant overexpression of PSDM6 (p = 0.004), TFRC (p = 0.01), CDK5R1 (p < 0.001), HSPG2 (p = 0.01), WDFY3 (p < 0.001), USP49 (p = 0.004) and GSE1 (p = 0.021) in AF patients vs HS.ConclusionsCDK5R1, GSE1, HSPG2 and WDFY3 resulted the best discriminatory genes both at methylation and gene expression level. Our results provide several candidate diagnostic biomarkers with the potential to advance precision medicine in AF.

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Section: Discussionmentioning

confidence: 56%

“…In particular, in these context, drugs and bioactive molecules, exerts their beneficial effects via epigenetic regulations. [67][68][69] Our findings further underscore the exciting potential of novel 'epidrugs' targeting the methylation-sensitive underpinnings of AF.…”

Section: Discussionmentioning

confidence: 61%

CDK5R1, GSE1, HSPG2 and WDFY3 as indirect epigenetic‐sensitive genes in atrial fibrillation

Infante,

Pepin,

Ruocco

et al. 2023

Eur J Clin Investigation

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“…Increased circulating IGF-1 in plasma reduces the risk of hypertension in women aged 30–55 [ 19 ]. Low serum IGF-1 levels predict the development of early cardiovascular disorders and hypertension [ 20 ]. The above data were based on experimental models or studies in adults.…”

Section: Discussionmentioning

confidence: 99%

“…The level of IGF-1 is regulated by many factors (insulin resistance, insulin levels, lipids, vitamin D3, hormones, metabolic syndrome, and inflammatory parameters) [ 20 , 21 , 22 , 23 , 24 ]. IGF-1 concentration in the upper reference range is associated with reduced blood pressure and vascular tone [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Expression of Insulin-like Growth Factor-1 (IGF-1), IGF-1 Receptor (IGF-1R), and Hypertension-Mediated Organ Damage (HMOD) Parameters in Leukocytes and Plasma of Children/Adolescents with Primary Hypertension

Grzywa-Czuba,

Trojanek,

Michałkiewicz

et al. 2024

JPM

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A decrease in IGF-1 is often linked to inflammation. Low systemic and local IGF-1 production and downregulation of IGF-1R expression may precede and predict PH development in children/adolescents. Leukocyte mRNA expression of IGF-1 and its receptor (IGF-1R) and plasma IGF-1 were measured in a group of 39 PH children/adolescents (29 boys and 10 girls) and 35 age-matched normotensive children (19 boys and 16 girls) using the RT-PCR and ELISA tests. The expression of the IGF-1R protein was assessed by flow cytometry. Plasma IGF-1 concentration was evaluated with ELISA. The expression of IGF-1 and IGF-1R and plasma concentrations of IGF-1 did not differ between groups. However, the PH children had a decreased percentage in IGF-1R-bearing lymphocytes (p = 0.02) and monocytes (p = 0.0003), as well as a low density of IGF-R in monocytes (p = 0.02). The IGF-1 expression was negatively correlated with pulse-wave velocity (PWV) (r = −0.49), systolic blood pressure (SBP) (−0.44), and carotid intima-media thickness (cIMT) (−0.43). The IGF-1R expression was negatively correlated with PWV (r = −0.42) and SBP (r = −0.41). Our results suggest that early subclinical hypertensive arterial injury is associated with lower activity of IGF-1-IGF-1R expression and loss of protective actions.

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“…IGF-1 promotes heart development, increases cardiac output, stroke volume, contractility, and ejection fraction. Human studies have also shown that low levels of serum free or total IGF-1 are associated with an increased risk of cardiovascular and cerebrovascular diseases ( 9 ). The role of IGF-1 in the body is becoming increasingly apparent.…”

Section: Introductionmentioning

confidence: 99%

Causal associations between insulin-like growth factor 1 and vitamin D levels: a two-sample bidirectional Mendelian randomization study

Gou,

Li,

Qiao

et al. 2023

Front. Nutr.

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BackgroundInsulin-like growth factor 1 (IGF-1) plays a vital role in the attainment and maintenance of bone mass throughout life and is closely related to the stature of children. 25-Hydroxyvitamin D (25-OHD) is an intermediate of vitamin D (Vit D) metabolism and a key indicator of Vit D nutritional status. Multiple studies have revealed that IGF-1 levels undergo a non-significant increase after Vit D supplementation. Here, we analyzed the causal and reverse causal relationships between 25-OHD and IGF-1 levels using Mendelian randomization (MR).MethodsTwo-sample MR was used to estimate an unconfounded bidirectional causal relationship between the level of IGF-1 and those of Vit D and 25-OHD. Single nucleotide polymorphisms (SNPs) were filtered from genome-wide association studies (GWAS) after a comprehensive search of the Integrative Epidemiology Unit GWAS database. Several MR methods were employed, including inverse-variance weighted (IVW) method, and a sensitivity analysis was undertaken to detect whether pleiotropy or heterogeneity biased the MR results.ResultsGenetically predicted IGF-1 was found to have a causal association with Vit D and serum 25-OHD levels, where Vit D and serum 25-OHD levels increased with increasing IGF-1 concentrations (Vit D: IVW β:0.021, 95% CI: 0.005–0.036, p = 7.74 × 10–3; 25-OHD: IVW β: 0.041, 95% CI: 0.026–0.057, p = 2.50 × 10–7). A reverse causal effect was also found, indicating Vit D and serum 25-OHD have a positive causal relationship with IGF-1 (Vit D: IVW β:0.182, 95% CI: 0.061–0.305, p = 3.25 × 10–3; 25-OHD: IVW β: 0.057, 95% CI = 0.017–0.096, p = 4.73 × 10–3). The sensitivity analysis showed that horizontal pleiotropy was unlikely to bias the causality in this study (MR-Egger: Vit D intercept p = 5.1 × 10–5, 25-OHD intercept p = 6.4 × 10–4 in forward analysis; Vit D intercept p = 6.6 × 10–4, 25-OHD intercept p = 1.9 × 10–3 in reverse analysis), and a leave-one-out analysis did not identify evidence of bias in the results.ConclusionThe results of the MR analysis provide evidence that IGF-1 has positive causal and reverse causal relationships with Vit D and serum 25-OHD, respectively, in European populations. Our findings also provide guidance for the prevention and treatment of short stature and other related diseases.

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New insights on the cardiovascular effects of IGF-1

Cited by 24 publications

References 223 publications

CDK5R1, GSE1, HSPG2 and WDFY3 as indirect epigenetic‐sensitive genes in atrial fibrillation

CDK5R1, GSE1, HSPG2 and WDFY3 as indirect epigenetic‐sensitive genes in atrial fibrillation

Association between Expression of Insulin-like Growth Factor-1 (IGF-1), IGF-1 Receptor (IGF-1R), and Hypertension-Mediated Organ Damage (HMOD) Parameters in Leukocytes and Plasma of Children/Adolescents with Primary Hypertension

Causal associations between insulin-like growth factor 1 and vitamin D levels: a two-sample bidirectional Mendelian randomization study

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