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Published in: BMC Cardiovascular Disorders 1/2021

Open Access 01-12-2021 | Arterial Occlusive Disease | Research article

Replication study reveals miR-483-5p as an important target in prevention of cardiometabolic disease

Authors: Widet Gallo, Filip Ottosson, Cecilia Kennbäck, Amra Jujic, Jonathan Lou S. Esguerra, Lena Eliasson, Olle Melander

Published in: BMC Cardiovascular Disorders | Issue 1/2021

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Abstract

Background

Alterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case–control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis.

Methods

We measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound.

Results

In cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06–3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06–3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007).

Conclusion

miR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease.
Literature
2.
go back to reference Federation ID. IDF Diabetes Atlas. 9th ed. Brussels: Belgium; 2019. p. 2019. Federation ID. IDF Diabetes Atlas. 9th ed. Brussels: Belgium; 2019. p. 2019.
3.
go back to reference Mendis S, Puska P, Norrving B, World Health O, World Heart F, World Stroke O, et al. In: Mendis S, et al., editors. Global atlas on cardiovascular disease prevention and control. Geneva: World Health Organization; 2011. Mendis S, Puska P, Norrving B, World Health O, World Heart F, World Stroke O, et al. In: Mendis S, et al., editors. Global atlas on cardiovascular disease prevention and control. Geneva: World Health Organization; 2011.
4.
go back to reference Eliasson L, Regazzi R. Micro(RNA) Management and Mismanagement of the Islet. J Mol Biol. 2020;432(5):1419–28.CrossRef Eliasson L, Regazzi R. Micro(RNA) Management and Mismanagement of the Islet. J Mol Biol. 2020;432(5):1419–28.CrossRef
5.
go back to reference World Health O. Definition, diagnosis and classification of diabetes mellitus and its complications : report of a WHO consultation. Part 1, Diagnosis and classification of diabetes mellitus. In. Geneva: World Health Organization; 1999. World Health O. Definition, diagnosis and classification of diabetes mellitus and its complications : report of a WHO consultation. Part 1, Diagnosis and classification of diabetes mellitus. In. Geneva: World Health Organization; 1999.
6.
go back to reference Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003;290(7):898–904.CrossRef Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003;290(7):898–904.CrossRef
7.
go back to reference Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414(6865):782–7.CrossRef Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414(6865):782–7.CrossRef
8.
go back to reference Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999;22(2):233–40.CrossRef Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999;22(2):233–40.CrossRef
9.
go back to reference Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol. 2013;9(9):513–21.CrossRef Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol. 2013;9(9):513–21.CrossRef
10.
go back to reference Eliasson L, Esguerra JLS. MicroRNA networks in pancreatic islet cells: normal function and type 2 diabetes. Diabetes. 2020;69(5):804–12.CrossRef Eliasson L, Esguerra JLS. MicroRNA networks in pancreatic islet cells: normal function and type 2 diabetes. Diabetes. 2020;69(5):804–12.CrossRef
11.
go back to reference Lu D, Thum T. RNA-based diagnostic and therapeutic strategies for cardiovascular disease. Nat Rev Cardiol. 2019;16(11):661–74.CrossRef Lu D, Thum T. RNA-based diagnostic and therapeutic strategies for cardiovascular disease. Nat Rev Cardiol. 2019;16(11):661–74.CrossRef
12.
go back to reference Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.CrossRef Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.CrossRef
13.
go back to reference Esguerra JLS, Nagao M, Ofori JK, Wendt A, Eliasson L. MicroRNAs in islet hormone secretion. Diabetes Obes Metab. 2018;20(Suppl 2):11–9.CrossRef Esguerra JLS, Nagao M, Ofori JK, Wendt A, Eliasson L. MicroRNAs in islet hormone secretion. Diabetes Obes Metab. 2018;20(Suppl 2):11–9.CrossRef
14.
go back to reference Ji C, Guo X. The clinical potential of circulating microRNAs in obesity. Nat Rev Endocrinol. 2019;15(12):731–43.CrossRef Ji C, Guo X. The clinical potential of circulating microRNAs in obesity. Nat Rev Endocrinol. 2019;15(12):731–43.CrossRef
15.
go back to reference Gallo W, Esguerra JLS, Eliasson L, Melander O. miR-483-5p associates with obesity and insulin resistance and independently associates with new onset diabetes mellitus and cardiovascular disease. PLoS ONE. 2018;13(11):e0206974.CrossRef Gallo W, Esguerra JLS, Eliasson L, Melander O. miR-483-5p associates with obesity and insulin resistance and independently associates with new onset diabetes mellitus and cardiovascular disease. PLoS ONE. 2018;13(11):e0206974.CrossRef
16.
go back to reference Gidlof O, Smith JG, Miyazu K, et al. Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction. In. BMC Cardiovasc Disord. Vol 13. 2013/03/02 ed2013:12. Gidlof O, Smith JG, Miyazu K, et al. Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction. In. BMC Cardiovasc Disord. Vol 13. 2013/03/02 ed2013:12.
17.
go back to reference Rosvall M, Persson M, Ostling G, et al. Risk factors for the progression of carotid intima-media thickness over a 16-year follow-up period: the Malmo Diet and Cancer Study. Atherosclerosis. 2015;239(2):615–21.CrossRef Rosvall M, Persson M, Ostling G, et al. Risk factors for the progression of carotid intima-media thickness over a 16-year follow-up period: the Malmo Diet and Cancer Study. Atherosclerosis. 2015;239(2):615–21.CrossRef
18.
go back to reference Enhörning S, Sjögren M, Hedblad B, Nilsson PM, Struck J, Melander O. Genetic vasopressin 1b receptor variance in overweight and diabetes mellitus. Eur J Endocrinol. 2016;174(1):69–75.CrossRef Enhörning S, Sjögren M, Hedblad B, Nilsson PM, Struck J, Melander O. Genetic vasopressin 1b receptor variance in overweight and diabetes mellitus. Eur J Endocrinol. 2016;174(1):69–75.CrossRef
19.
go back to reference Ludvigsson JF, Andersson E, Ekbom A, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.CrossRef Ludvigsson JF, Andersson E, Ekbom A, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.CrossRef
20.
go back to reference Ottosson F, Smith E, Melander O, Fernandez C. Altered asparagine and glutamate homeostasis precede coronary artery disease and type 2 diabetes. J Clin Endocrinol Metab. 2018;103(8):3060–9.CrossRef Ottosson F, Smith E, Melander O, Fernandez C. Altered asparagine and glutamate homeostasis precede coronary artery disease and type 2 diabetes. J Clin Endocrinol Metab. 2018;103(8):3060–9.CrossRef
21.
go back to reference Ottosson F, Brunkwall L, Ericson U, et al. Connection between BMI-related plasma metabolite profile and gut microbiota. J Clin Endocrinol Metab. 2018;103(4):1491–501.CrossRef Ottosson F, Brunkwall L, Ericson U, et al. Connection between BMI-related plasma metabolite profile and gut microbiota. J Clin Endocrinol Metab. 2018;103(4):1491–501.CrossRef
22.
go back to reference Fu H, Tie Y, Xu C, et al. Identification of human fetal liver miRNAs by a novel method. FEBS Lett. 2005;579(17):3849–54.CrossRef Fu H, Tie Y, Xu C, et al. Identification of human fetal liver miRNAs by a novel method. FEBS Lett. 2005;579(17):3849–54.CrossRef
23.
go back to reference Ma N, Wang X, Qiao Y, et al. Coexpression of an intronic microRNA and its host gene reveals a potential role for miR-483-5p as an IGF2 partner. Mol Cell Endocrinol. 2011;333(1):96–101.CrossRef Ma N, Wang X, Qiao Y, et al. Coexpression of an intronic microRNA and its host gene reveals a potential role for miR-483-5p as an IGF2 partner. Mol Cell Endocrinol. 2011;333(1):96–101.CrossRef
24.
go back to reference Roth SM, Schrager MA, Metter EJ, et al. IGF2 genotype and obesity in men and women across the adult age span. Int J Obes Relat Metab Disord. 2002;26(4):585–7.CrossRef Roth SM, Schrager MA, Metter EJ, et al. IGF2 genotype and obesity in men and women across the adult age span. Int J Obes Relat Metab Disord. 2002;26(4):585–7.CrossRef
25.
go back to reference Sandhu MS, Gibson JM, Heald AH, Dunger DB, Wareham NJ. Low circulating IGF-II concentrations predict weight gain and obesity in humans. Diabetes. 2003;52(6):1403–8.CrossRef Sandhu MS, Gibson JM, Heald AH, Dunger DB, Wareham NJ. Low circulating IGF-II concentrations predict weight gain and obesity in humans. Diabetes. 2003;52(6):1403–8.CrossRef
26.
go back to reference Szabo G, Csak T. Role of MicroRNAs in NAFLD/NASH. Dig Dis Sci. 2016;61(5):1314–24.CrossRef Szabo G, Csak T. Role of MicroRNAs in NAFLD/NASH. Dig Dis Sci. 2016;61(5):1314–24.CrossRef
27.
go back to reference Plichart M, Celermajer DS, Zureik M, et al. Carotid intima-media thickness in plaque-free site, carotid plaques and coronary heart disease risk prediction in older adults. The Three-City Study. Atherosclerosis. 2011;219(2):917–24.CrossRef Plichart M, Celermajer DS, Zureik M, et al. Carotid intima-media thickness in plaque-free site, carotid plaques and coronary heart disease risk prediction in older adults. The Three-City Study. Atherosclerosis. 2011;219(2):917–24.CrossRef
28.
go back to reference Cao JJ, Arnold AM, Manolio TA, et al. Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study. Circulation. 2007;116(1):32–8.CrossRef Cao JJ, Arnold AM, Manolio TA, et al. Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study. Circulation. 2007;116(1):32–8.CrossRef
29.
go back to reference Ebrahim S, Papacosta O, Whincup P, et al. Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study. Stroke. 1999;30(4):841–50.CrossRef Ebrahim S, Papacosta O, Whincup P, et al. Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study. Stroke. 1999;30(4):841–50.CrossRef
30.
go back to reference Lind L, Gigante B, Borne Y, et al. The plasma protein profile and cardiovascular risk differ between intima-media thickness of the common carotid artery and the bulb: a meta-analysis and a longitudinal evaluation. Atherosclerosis. 2020;295:25–30.CrossRef Lind L, Gigante B, Borne Y, et al. The plasma protein profile and cardiovascular risk differ between intima-media thickness of the common carotid artery and the bulb: a meta-analysis and a longitudinal evaluation. Atherosclerosis. 2020;295:25–30.CrossRef
Metadata
Title
Replication study reveals miR-483-5p as an important target in prevention of cardiometabolic disease
Authors
Widet Gallo
Filip Ottosson
Cecilia Kennbäck
Amra Jujic
Jonathan Lou S. Esguerra
Lena Eliasson
Olle Melander
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2021
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-021-01964-0

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