TY - JOUR
T1 - Sex-specific microRNAs in women with diabetes and left ventricular diastolic dysfunction or HFpEF associate with microvascular injury
AU - Florijn, Barend W.
AU - Valstar, Gideon B.
AU - Duijs, Jacques M.G.J.
AU - Menken, Roxana
AU - Cramer, Maarten J.
AU - Teske, Arco J.
AU - Ghossein-Doha, Chahinda
AU - Rutten, Frans H.
AU - Spaanderman, Marc E.A.
AU - den Ruijter, Hester M.
AU - Bijkerk, Roel
AU - van Zonneveld, Anton Jan
PY - 2020/8/18
Y1 - 2020/8/18
N2 - Left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF) are microcirculation defects following diabetes mellitus (DM). Unrecognized HFpEF is more prevalent in women with diabetes compared to men with diabetes and therefore sex-specific diagnostic strategies are needed. Previously, we demonstrated altered plasma miRs in DM patients with microvascular injury [defined by elevated plasma Angiopoietin-2 (Ang-2) levels]. This study hypothesized the presence of sex-differences in plasma miRs and Ang-2 in diabetic (female) patients with LVDD or HFpEF. After a pilot study, we assessed 16 plasma miRs in patients with LVDD (n = 122), controls (n = 244) and female diabetic patients (n = 10). Subsequently, among these miRs we selected and measured plasma miR-34a, -224 and -452 in diabetic HFpEF patients (n = 53) and controls (n = 52). In LVDD patients, miR-34a associated with Ang-2 levels (R2 0.04, R = 0.21, p = 0.001, 95% CI 0.103–0.312), with plasma levels being diminished in patients with DM, while women with an eGFR < 60 ml/min and LVDD had lower levels of miR-34a, -224 and -452 compared to women without an eGFR < 60 ml/min without LVDD. In diabetic HFpEF women (n = 28), plasma Ang-2 levels and the X-chromosome located miR-224/452 cluster increased compared to men. We conclude that plasma miR-34a, -224 and -452 display an association with the microvascular injury marker Ang-2 and are particularly targeted to women with LVDD or HFpEF.
AB - Left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF) are microcirculation defects following diabetes mellitus (DM). Unrecognized HFpEF is more prevalent in women with diabetes compared to men with diabetes and therefore sex-specific diagnostic strategies are needed. Previously, we demonstrated altered plasma miRs in DM patients with microvascular injury [defined by elevated plasma Angiopoietin-2 (Ang-2) levels]. This study hypothesized the presence of sex-differences in plasma miRs and Ang-2 in diabetic (female) patients with LVDD or HFpEF. After a pilot study, we assessed 16 plasma miRs in patients with LVDD (n = 122), controls (n = 244) and female diabetic patients (n = 10). Subsequently, among these miRs we selected and measured plasma miR-34a, -224 and -452 in diabetic HFpEF patients (n = 53) and controls (n = 52). In LVDD patients, miR-34a associated with Ang-2 levels (R2 0.04, R = 0.21, p = 0.001, 95% CI 0.103–0.312), with plasma levels being diminished in patients with DM, while women with an eGFR < 60 ml/min and LVDD had lower levels of miR-34a, -224 and -452 compared to women without an eGFR < 60 ml/min without LVDD. In diabetic HFpEF women (n = 28), plasma Ang-2 levels and the X-chromosome located miR-224/452 cluster increased compared to men. We conclude that plasma miR-34a, -224 and -452 display an association with the microvascular injury marker Ang-2 and are particularly targeted to women with LVDD or HFpEF.
KW - Adult
KW - Aged
KW - Angiopoietin-2/analysis
KW - Biomarkers/blood
KW - Diabetes Complications/genetics
KW - Diabetes Mellitus/genetics
KW - Female
KW - Heart Failure/genetics
KW - Humans
KW - Male
KW - MicroRNAs/genetics
KW - Middle Aged
KW - Pilot Projects
KW - Sex Characteristics
KW - Stroke Volume/genetics
KW - Ventricular Dysfunction, Left/genetics
KW - Ventricular Function, Left/genetics
UR - http://www.scopus.com/inward/record.url?scp=85089466788&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-70848-8
DO - 10.1038/s41598-020-70848-8
M3 - Article
C2 - 32811874
AN - SCOPUS:85089466788
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 13945
ER -