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. 2018 Mar 1;17(1):35.
doi: 10.1186/s12944-018-0681-0.

Increased plasma and adipose tissue levels of ANGPTL8/Betatrophin and ANGPTL4 in people with hypertension

Mohamed Abu-Farha  1 , Preethi Cherian  2 , Mohamed G Qaddoumi  3 , Irina AlKhairi  2 , Devarajan Sriraman  4 , Muath Alanbaei  5 , Jehad Abubaker  6
Affiliations

Increased plasma and adipose tissue levels of ANGPTL8/Betatrophin and ANGPTL4 in people with hypertension

Mohamed Abu-Farha et al. Lipids Health Dis. .

Abstract

Background: Hypertension is a risk factor for both cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Angiopoietin-like proteins (ANGPTLs), mainly ANGPTL3, ANGPTL4 and ANGPTL8, are associated with increased plasma lipid content due to their role in regulating the activity of lipoprotein lipase, a key enzyme in metabolism of the lipoprotein in circulation. Dyslipidaemia is a risk factor for hypertension development; however, the roles of ANGPTL3, ANGPTL4 and ANGPTL8 in subjects with hypertension have not yet been established. This study compared the plasma and adipose tissue levels of ANGPTL3, ANGPTL4 and ANGPTL8 in age- and body mass index-matched subjects with and without hypertension.

Methods: A total of 119 subjects, including 69 hypertensive and 50 non-hypertensive subjects, were enrolled. ANGPTL3, ANGPTL4 and ANGPTL8 plasma levels were measured by ELISA, whereas their levels in adipose tissue were assessed via real-time PCR.

Results: We found that ANGPTL4 (202.49 ± 17.44 ng/mL vs. 160.64 ± 10.36 ng/mL, p = 0.04) and ANGPTL8 levels (2310.96 ± 194.88 pg/mL vs. 1583.35 ± 138.27 pg/mL, p = 0.001) were higher in hypertensive subjects than non-hypertensive subjects. However, ANGPTL3 levels were not significantly different between the two populations. Similarly, ANGPTL4 and ANGPTL8 levels were also elevated in subjects with T2D and hypertension than in those with T2D but not hypertension. Additionally, people with highest tertiles of ANGPTL8 had higher odds of having hypertension (odd ratio [OR] = 3.8, 95% confidence interval [CI] = (1.5-9.8), p-Value = 0.005. Similar to its plasma levels, ANGPTL4 and ANGPTL8 were higher in adipose tissue.

Conclusions: In conclusion, our data illustrate that ANGPTL4 and ANGPTL8 levels in both plasma and adipose tissues are increased in subjects with hypertension. The elevated levels of ANGPTL4 and ANGPTL8 in hypertensive subjects highlight their potential involvement, their potential role as biomarkers for hypertension and their therapeutic value in hypertension given their roles in regulating lipid metabolism.

Keywords: Angiopoietin-like proteins; Hypertension; Type-2 diabetes.

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Conflict of interest statement

Ethics approval and consent to participate

All subjects signed a written informed consent before their participation in the study, which was approved by the Ethical Review Board of Dasman Diabetes Institute (number RA-2011-03) and abiding with the guideline ethical declaration of Helsinki.

Consent for publication

“Not applicable”

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Plasma levels of angiopoietin-like protein 3 (ANGPTL3), ANGPTL4 and ANGPTL8 in the whole population. a: Plasma levels of ANGPTL3 in non-hypertensive vs. hypertensive subjects as measured by ELISA. b: Plasma levels of ANGPTL4 in non-hypertensive vs. hypertensive subjects as measured by ELISA. c: Plasma levels of ANGPTL8 in non-hypertensive vs. hypertensive subjects as measured by ELISA. * p < 0.05, as determined using Student’s t-test
Fig. 2
Fig. 2
ANGPTL3, ANGPTL4 and ANGPTL8 plasma levels in hypertensive and non-hypertensive type 2 diabetes (T2D) subjects. a: Plasma levels of ANGPTL3 in T2D subjects without hypertension vs. those with hypertension as measured by ELISA. b: Plasma levels of ANGPTL4 in T2D subjects without hypertension vs. those with hypertension as measured by ELISA. c: Plasma levels of ANGPTL8 in T2D subjects without hypertension vs. those with hypertension as measured by ELISA. * p < 0.05, as determined using Student’s t-test
Fig. 3
Fig. 3
Plasma levels of ANGPTL3, ANGPTL4 and ANGPTL8 in non-diabetic subjects with and without hypertension. a: Plasma levels of ANGPTL3 in non-diabetic subjects without hypertension vs. those with hypertension as measured by ELISA. b: Plasma levels of ANGPTL4 in non-diabetic subjects without hypertension vs. those with hypertension as measured by ELISA. c: Plasma levels of ANGPTL8 in non-diabetic subjects without hypertension vs. those with hypertension as measured by ELISA. * p < 0.05, as determined using Student’s t-test
Fig. 4
Fig. 4
Adipose tissue levels of ANGPTL3, ANGPTL4 and ANGPTL8 in the whole population. a: Adipose tissue gene expression of ANGPTL3 in subjects without hypertension vs. those with hypertension in the whole population as measured by real-time PCR. b: Adipose tissue gene expression of ANGPTL4 in subjects without hypertension vs. those with hypertension in the whole population as measured by real-time PCR. c: Adipose tissue gene expression of ANGPTL8 in subjects without hypertension vs. those with hypertension in the whole population as measured by real-time PCR. * p < 0.05, as determined using Student’s t-test
Fig. 5
Fig. 5
Adipose tissue expression of ANGPTL3, ANGPTL4 and ANGPTL8 in T2D subjects with and without hypertension. a: Adipose tissue gene expression of ANGPTL3 in T2D subjects without hypertension vs. those with hypertension as measured by real-time PCR. b: Adipose tissue gene expression of ANGPTL4 in T2D subjects without hypertension vs. those with hypertension as measured by real-time PCR. c: Adipose tissue gene expression of ANGPTL8 in T2D subjects without hypertension vs. those with hypertension as measured by real-time PCR. * p < 0.05, as determined using Student’s t-test
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