Galectin-4 levels in hospitalized versus non-hospitalized subjects with obesity: the Malmö Preventive Project

Korduner, Johan; Holm, Hannes; Jujić, Amra; Melander, Olle; Pareek, Manan; Molvin, John; Råstam, Lennart; Lindblad, Ulf; Daka, Bledar; Léosdottír, Margret; Nilsson, Peter M.; Bachus, Erasmus; Olsen, Michael Hecht; Magnusson, Martin

doi:10.1186/s12933-022-01559-9

Cited by 4 publications

(3 citation statements)

References 51 publications

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“…Another study compared heart failure patients to controls both recruited in the outpatient clinic at Karolinska University Hospital, finding galectin-4 to be significantly associated with heart failure (HR = 2.6; FDR adjusted p-value 0.005) [ 33 ]. In addition, galectin-4 has been reported to be associated with hospitalization linked to obesity [ 34 ] and ST-segment elevation myocardial infarction [ 35 ]. All listed reports are in line with our finding of galectin-4’s association with CHD.…”

Section: Discussionmentioning

confidence: 99%

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study

Elhadad,

del C. Gómez-Alonso,

Chen

et al. 2024

Cardiovasc Diabetol

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Background and aims Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis. Methods The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model. Results In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30–1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09–1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (β = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways. Conclusions Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.

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Section: Discussionmentioning

confidence: 99%

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study

Elhadad,

del C. Gómez-Alonso,

Chen

et al. 2024

Cardiovasc Diabetol

View full text Add to dashboard Cite

show abstract

“…Another study compared heart failure patients to controls both recruited in the outpatient clinic at Karolinska University Hospital, nding galectin-4 to be signi cantly associated with heart failure (HR = 2.6; FDR adjusted pvalue 0.005) (32). In addition, galectin-4 has been reported to be associated with hospitalization linked to obesity (33) and ST-segment elevation myocardial infarction (34). All listed reports are in line with our nding of galectin-4's association with CHD.…”

Section: Discussionmentioning

confidence: 99%

Plasma Proteome Association with Coronary Heart Disease and Carotid Intima Media Thickness: results from the KORA F4 study

Elhadad,

Gómez-Alonso,

Chen

et al. 2023

Preprint

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Background and aims: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis. Methods: The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model. Results: In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.3 - 1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09 - 1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (ꞵ = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways. Conclusions: Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.

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“…Obesity is strongly associated with the progression of cardiovascular diseases and diabetes. Elevated galectin-4 levels were associated with a higher probability of obesity-associated hospitalization in diabetic patients (211). Thus, galectin-4 could be a risk factor in the pathogenesis of diabetes mellitus.…”

Section: Galectin-4mentioning

confidence: 92%

Galectin functions in cancer-associated inflammation and thrombosis

Kruk

Braun²,

Cosset³

et al. 2023

Front. Cardiovasc. Med.

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Galectins are carbohydrate-binding proteins that regulate many cellular functions including proliferation, adhesion, migration, and phagocytosis. Increasing experimental and clinical evidence indicates that galectins influence many steps of cancer development by inducing the recruitment of immune cells to the inflammatory sites and modulating the effector function of neutrophils, monocytes, and lymphocytes. Recent studies described that different isoforms of galectins can induce platelet adhesion, aggregation, and granule release through the interaction with platelet-specific glycoproteins and integrins. Patients with cancer and/or deep-venous thrombosis have increased levels of galectins in the vasculature, suggesting that these proteins could be important contributors to cancer-associated inflammation and thrombosis. In this review, we summarize the pathological role of galectins in inflammatory and thrombotic events, influencing tumor progression and metastasis. We also discuss the potential of anti-cancer therapies targeting galectins in the pathological context of cancer-associated inflammation and thrombosis.

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Galectin-4 levels in hospitalized versus non-hospitalized subjects with obesity: the Malmö Preventive Project

Cited by 4 publications

References 51 publications

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study

Plasma Proteome Association with Coronary Heart Disease and Carotid Intima Media Thickness: results from the KORA F4 study

Galectin functions in cancer-associated inflammation and thrombosis

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