Abstract
BackgroundHypertension 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.MethodsA 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.ResultsWe 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.ConclusionsIn 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.
Highlights
Hypertension is a risk factor for both cardiovascular diseases (CVDs) and type 2 diabetes (T2D)
We recently illustrated that angiopoietin-like protein 8 (ANGPTL8), known as betatrophin, is strongly associated with high sensitivity C-reactive protein (HsCRP) levels and an increased incidence of metabolic syndrome [3]
ANGPTL3, ANGPTL4 and ANGPTL8 regulate the activity of lipoprotein lipase (LPL), a key enzyme in the hydrolysis of plasma lipoproteins [9,10,11]
Summary
Hypertension is a risk factor for both cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Better understanding of various factors involved in hypertension development will lead to improved early detection and prevention of the onset of hypertension, T2D and CVDs. We recently illustrated that angiopoietin-like protein 8 (ANGPTL8), known as betatrophin, is strongly associated with high sensitivity C-reactive protein (HsCRP) levels and an increased incidence of metabolic syndrome [3]. We recently illustrated that angiopoietin-like protein 8 (ANGPTL8), known as betatrophin, is strongly associated with high sensitivity C-reactive protein (HsCRP) levels and an increased incidence of metabolic syndrome [3] Certain biomarkers such as high-sensitivity Creactive protein (HsCRP) can act as early signs of increased risks for hypertension and T2D development [4, 5]. Recent studies involving examination of mutations in the ANGPTL4 gene revealed that these mutations were associated with lower plasma lipid levels and reduced cardiovascular risk [12]. We examined the plasma and adipose tissue levels of ANGPTL3, ANGPTL4 and ANGPTL8 in subjects with or without hypertension using ELISA and real-time PCR
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