RETRACTED ARTICLE: Effect of rosuvastatin on fasting and postprandial endothelial biomarker levels and microvascular reactivity in patients with type 2 diabetes and dyslipidemia: a preliminary report

Abstract

BackgroundThe cardiovascular benefits of statins have been proven, but their effect on circulation in small vessels has not been examined fully. We investigated the effect of 20 mg rosuvastatin on biomarkers, including paraoxonase-1 (PON-1) and asymmetric dimethylarginine (ADMA), and on microvascular reactivity.MethodWe enrolled 20 dyslipidemic patients with type 2 diabetes and 20 age- and body mass index (BMI)-matched healthy controls. Rosuvastatin (20 mg/day) was given to the patient group for 12 weeks. Biochemical parameters, including PON-1 and ADMA, were compared between the patient and control groups, and before and after rosuvastatin treatment in the patient group. Fasting and 2 h postprandial levels of PON-1 and ADMA after mixed-meal challenge were also compared. Microvascular reactivity in a peripheral artery was examined using laser Doppler flowmetry.ResultsThe respective mean ± standard deviation of age and BMI were 50.1 ± 3.8 year and 25.8 ± 3.7 kg/m2 in the patients and 50.2 ± 3.2 year and 25.4 ± 3.4 kg/m2 in the controls. The patient group had worse profiles of cardiometabolic biomarkers, including PON-1 and ADMA, than the controls. In the patients treated with 20 mg rosuvastatin, low-density lipoprotein (LDL)-cholesterol decreased from 147.2 ± 26.5 to 68.3 ± 24.5 mg/dL and high-density lipoprotein (HDL)-cholesterol increased from 42.4 ± 5.2 to 44.7 ± 6.2 mg/dL (both P < 0.05). Both fasting and 2 h postprandial levels of PON-1 increased and those of ADMA decreased after treatment with rosuvastatin for 12 weeks. The changes in postprandial levels of both biomarkers were greater than those after fasting. Microcirculation assessed as reactive hyperemia in the patients after an ischemic challenge increased significantly from 335.3 ± 123.4 to 402.7 ± 133.4% after rosuvastatin treatment. The postprandial changes in the biomarkers were significantly associated with improvement of microvascular reactivity.ConclusionsRosuvastatin treatment for 12 weeks improved microvascular reactivity with concomitant beneficial changes in the postprandial levels of PON-1 and ADMA. These results suggest that rosuvastatin improves the postprandial cardiometabolic milieu in type 2 diabetes. Trial registration ClinicalTrials.gov: NCT02185963 (July 7, 2014)Electronic supplementary materialThe online version of this article (10.1186/s12933-017-0629-0) contains supplementary material, which is available to authorized users.

Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies

“…As mentioned previously, accelerated atherosclerosis in T2DM is also associated with decreased activity of PON-1. Rosuvastatin, a class of statins, was shown to improve microvascular reactivity with associated beneficial changes in the postprandial levels of ADMA and PON-1 [ 121 ]. Furthermore, a continuous intravenous infusion of glucagon-like peptide-1 (GLP-1) analogs was reported to improve the blood glucose-independent vascular endothelial dysfunction in T2DM patients with stable CAD [ 122 ].…”

Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and homoarginine (hArg): the ADMA, SDMA and hArg paradoxes

“…PON-1 is thought to be associated with lipid peroxidation. In patients suffering from T2DM and dyslipidemia, 12-weeks treatment with rosuvastatin was reported to increase serum PON-1 activity and to lower plasma ADMA concentration [ 12 ]. Yet, a correlation between PON-1 and ADMA seems not to have occurred in that study at baseline or after rosuvastatin treatment.…”

Correction to: Diabetes, cardiovascular disease and the microcirculation

“…Following publication of the original article [ 1 ], it has been brought to our attention that the article in Ref. [ 72 ] was retracted in March 2019.…”

“…“In addition to anti-diabetes agents, statins were reported to improve endothelial dysfunction and microvascular reactivity in patients with T2DM and dyslipidaemia, suggesting positive outcomes on CV morbidity and mortality of these class of drugs [ 72 ].”…”