TY - JOUR
T1 - Acute metabolic influences on the natriuretic peptide system in humans
AU - Arora, Pankaj
AU - Wu, Connie
AU - Hamid, Tariq
AU - Arora, Garima
AU - Agha, Obiajulu
AU - Allen, Kaitlin
AU - Tainsh, Robert E.T.
AU - Hu, Dongjian
AU - Ryan, Romy A.
AU - Domian, Ibrahim J.
AU - Buys, Emmanuel S.
AU - Bloch, Donald B.
AU - Prabhu, Sumanth D.
AU - Bloch, Kenneth D.
AU - Newton-Cheh, Christopher
AU - Wang, Thomas J.
N1 - Publisher Copyright:
© 2016 American College of Cardiology Foundation.
PY - 2016/2/23
Y1 - 2016/2/23
N2 - Background The cardiac natriuretic peptides (NPs), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), have central roles in sodium and blood pressure regulation. Extracardiac factors (e.g., obesity and diabetes) influence NP production, potentially altering cardiovascular responses to volume and pressure stress. Objectives This study examined the effects of acute carbohydrate intake on the NP system in humans, and investigated underlying mechanisms. Methods Normotensive subjects (N = 33) were given a high-carbohydrate shake. Venous blood was sampled to measure N-terminal (NT)-proANP and NT-proBNP levels. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and HepG2 cells were treated with glucose, and expression levels of NPs and micro ribonucleic acid 425 (miR-425), a negative regulator of ANP, were examined. The role of nuclear factor kappa B (NF-κB) in the glucose-mediated effects was investigated using a NF-κB inhibitor and expression plasmids encoding NF-κB subunits. Results We observed a 27% reduction in the levels of circulating NT-proANP (p < 0.001, maximal at 6 h) after carbohydrate challenge, with no effect on NT-proBNP levels in our human subjects. Glucose treatment of hESC-CMs for 6 h and 24 h increased levels of the primary transcript of miR-425 (pri-miR-425) and mature miR-425. A corresponding decrease in NPPA messenger RNA levels was also observed at both time points. Overexpression of NF-κB subunits in H9c2 cardiomyocytes increased miR-425 levels, whereas inhibition of NF-κB abrogated the glucose-mediated increase in pri-miR-425 levels in HepG2 cells. Conclusions Acute carbohydrate challenge is associated with a reduction in ANP production. The mechanism appears to involve a glucose-induced increase in the expression of miR-425, mediated by NF-κB signaling.
AB - Background The cardiac natriuretic peptides (NPs), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), have central roles in sodium and blood pressure regulation. Extracardiac factors (e.g., obesity and diabetes) influence NP production, potentially altering cardiovascular responses to volume and pressure stress. Objectives This study examined the effects of acute carbohydrate intake on the NP system in humans, and investigated underlying mechanisms. Methods Normotensive subjects (N = 33) were given a high-carbohydrate shake. Venous blood was sampled to measure N-terminal (NT)-proANP and NT-proBNP levels. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and HepG2 cells were treated with glucose, and expression levels of NPs and micro ribonucleic acid 425 (miR-425), a negative regulator of ANP, were examined. The role of nuclear factor kappa B (NF-κB) in the glucose-mediated effects was investigated using a NF-κB inhibitor and expression plasmids encoding NF-κB subunits. Results We observed a 27% reduction in the levels of circulating NT-proANP (p < 0.001, maximal at 6 h) after carbohydrate challenge, with no effect on NT-proBNP levels in our human subjects. Glucose treatment of hESC-CMs for 6 h and 24 h increased levels of the primary transcript of miR-425 (pri-miR-425) and mature miR-425. A corresponding decrease in NPPA messenger RNA levels was also observed at both time points. Overexpression of NF-κB subunits in H9c2 cardiomyocytes increased miR-425 levels, whereas inhibition of NF-κB abrogated the glucose-mediated increase in pri-miR-425 levels in HepG2 cells. Conclusions Acute carbohydrate challenge is associated with a reduction in ANP production. The mechanism appears to involve a glucose-induced increase in the expression of miR-425, mediated by NF-κB signaling.
KW - cardiomyocyte
KW - glucose
KW - micro ribonucleic acid
KW - obesity
UR - http://www.scopus.com/inward/record.url?scp=85013725567&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2015.11.049
DO - 10.1016/j.jacc.2015.11.049
M3 - Article
C2 - 26892417
AN - SCOPUS:85013725567
SN - 0735-1097
VL - 67
SP - 804
EP - 812
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 7
ER -