TY - JOUR
T1 - Angiotensin II regulates microRNA-132/-212 in hypertensive rats and humans
AU - Eskildsen, Tilde V
AU - Jeppesen, Pia L
AU - Schneider, Mikael
AU - Nossent, Anne Y
AU - Sandberg, Maria B
AU - Hansen, Pernille B L
AU - Jensen, Charlotte H
AU - Hansen, Maria L
AU - Marcussen, Niels
AU - Rasmussen, Lars M
AU - Bie, Peter
AU - Andersen, Ditte C
AU - Sheikh, Søren P
PY - 2013/5/27
Y1 - 2013/5/27
N2 - MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, are emerging as key regulators in cardiovascular development and disease. MiRNAs are involved in cardiac hypertrophy, heart failure and remodeling following cardiac infarction; however, miRNAs involved in hypertension have not been thoroughly investigated. We have recently reported that specific miRNAs play an integral role in Angiotensin II receptor (AT1R) signaling, especially after activation of the Gαq signaling pathway. Since AT1R blockers are widely used to treat hypertension, we undertook a detailed analysis of potential miRNAs involved in Angiotensin II (AngII) mediated hypertension in rats and hypertensive patients, using miRNA microarray and qPCR analysis. The miR-132 and miR-212 are highly increased in the heart, aortic wall and kidney of rats with hypertension (159 ± 12 mm Hg) and cardiac hypertrophy following chronic AngII infusion. In addition, activation of the endothelin receptor, another Gαq coupled receptor, also increased miR-132 and miR-212. We sought to extend these observations using human samples by reasoning that AT1R blockers may decrease miR-132 and miR-212. We analyzed tissue samples of mammary artery obtained from surplus arterial tissue after coronary bypass operations. Indeed, we found a decrease in expression levels of miR-132 and miR-212 in human arteries from bypass-operated patients treated with AT1R blockers, whereas treatment with β-blockers had no effect. Taken together, these data suggest that miR-132 and miR-212 are involved in AngII induced hypertension, providing a new perspective in hypertensive disease mechanisms.
AB - MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, are emerging as key regulators in cardiovascular development and disease. MiRNAs are involved in cardiac hypertrophy, heart failure and remodeling following cardiac infarction; however, miRNAs involved in hypertension have not been thoroughly investigated. We have recently reported that specific miRNAs play an integral role in Angiotensin II receptor (AT1R) signaling, especially after activation of the Gαq signaling pathway. Since AT1R blockers are widely used to treat hypertension, we undertook a detailed analysis of potential miRNAs involved in Angiotensin II (AngII) mediated hypertension in rats and hypertensive patients, using miRNA microarray and qPCR analysis. The miR-132 and miR-212 are highly increased in the heart, aortic wall and kidney of rats with hypertension (159 ± 12 mm Hg) and cardiac hypertrophy following chronic AngII infusion. In addition, activation of the endothelin receptor, another Gαq coupled receptor, also increased miR-132 and miR-212. We sought to extend these observations using human samples by reasoning that AT1R blockers may decrease miR-132 and miR-212. We analyzed tissue samples of mammary artery obtained from surplus arterial tissue after coronary bypass operations. Indeed, we found a decrease in expression levels of miR-132 and miR-212 in human arteries from bypass-operated patients treated with AT1R blockers, whereas treatment with β-blockers had no effect. Taken together, these data suggest that miR-132 and miR-212 are involved in AngII induced hypertension, providing a new perspective in hypertensive disease mechanisms.
KW - AT1 receptor blocker
KW - AT1R
KW - Angiotensin II
KW - Hypertension
KW - microRNA
KW - Angiotensin II Type 1 Receptor Blockers/pharmacology
KW - Angiotensin II/pharmacology
KW - Animals
KW - Blood Pressure/drug effects
KW - Cardiomegaly/genetics
KW - Disease Models, Animal
KW - Endothelin-1
KW - Female
KW - Fibrosis
KW - Gene Expression Regulation/drug effects
KW - Humans
KW - Hypertension/genetics
KW - Mice
KW - Mice, Inbred C57BL
KW - MicroRNAs/genetics
KW - Oligonucleotide Array Sequence Analysis
KW - Organ Specificity/drug effects
KW - Rats, Sprague-Dawley
KW - Reproducibility of Results
KW - Vasoconstrictor Agents
UR - http://www.mendeley.com/research/angiotensin-ii-regulates-microrna132212-hypertensive-rats-humans
U2 - 10.3390/ijms140611190
DO - 10.3390/ijms140611190
M3 - Journal article
C2 - 23712358
SN - 1422-0067
VL - 14
SP - 11190
EP - 11207
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 6
ER -