BIOMAT Database Logo BIOMAT Database Logo

Resveratrol induces mitochondrial biogenesis and ameliorates Ang II-induced cardiac remodeling in transgenic rats harboring human renin and angiotensinogen genes. 2010

Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.

There is compelling evidence to indicate an important role for increased local renin-angiotensin system activity in the pathogenesis of cardiac hypertrophy and heart failure. Resveratrol is a natural polyphenol that activates SIRT1, a novel cardioprotective and longevity factor having NAD(+)-dependent histone deacetylase activity. We tested the hypothesis whether resveratrol could prevent from angiotensin II (Ang II)-induced cardiovascular damage. Four-week-old double transgenic rats harboring human renin and human angiotensinogen genes (dTGR) were treated for 4 weeks either with SIRT1 activator resveratrol or SIRT1 inhibitor nicotinamide. Untreated dTGR and their normotensive Sprague-Dawley control rats (SD) received vehicle. Untreated dTGR developed severe hypertension as well as cardiac hypertrophy, and showed pronounced cardiovascular mortality compared with normotensive SD rats. Resveratrol slightly but significantly decreased blood pressure, ameliorated cardiac hypertrophy and prevented completely Ang II-induced mortality, whereas nicotinamide increased blood pressure without significantly influencing cardiac hypertrophy or survival. Resveratrol decreased cardiac ANP mRNA expression and induced cardiac mRNA expressions of mitochondrial biogenesis markers peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha), mitochondrial transcription factor (Tfam), nuclear respiratory factor 1 (NRF-1) and cytochrome c oxidase subunit 4 (cox4). Resveratrol dose-dependently increased SIRT1 activity in vitro. Our findings suggest that the beneficial effects of SIRT1 activator resveratrol on Ang II-induced cardiac remodeling are mediated by blood pressure-dependent pathways and are linked to increased mitochondrial biogenesis.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D008297 Male Males
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D012083 Renin A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19. Angiotensin-Forming Enzyme,Angiotensinogenase,Big Renin,Cryorenin,Inactive Renin,Pre-Prorenin,Preprorenin,Prorenin,Angiotensin Forming Enzyme,Pre Prorenin,Renin, Big,Renin, Inactive
D012084 Renin-Angiotensin System A BLOOD PRESSURE regulating system of interacting components that include RENIN; ANGIOTENSINOGEN; ANGIOTENSIN CONVERTING ENZYME; ANGIOTENSIN I; ANGIOTENSIN II; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming ANGIOTENSIN I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to ANGIOTENSIN II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal VASCULAR SMOOTH MUSCLE, leading to retention of salt and water in the KIDNEY and increased arterial blood pressure. In addition, angiotensin II stimulates the release of ALDOSTERONE from the ADRENAL CORTEX, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down BRADYKININ, a powerful vasodilator and component of the KALLIKREIN-KININ SYSTEM. Renin-Angiotensin-Aldosterone System,Renin Angiotensin Aldosterone System,Renin Angiotensin System,System, Renin-Angiotensin,System, Renin-Angiotensin-Aldosterone
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D005796 Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Cistron,Gene,Genetic Materials,Cistrons,Genetic Material,Material, Genetic,Materials, Genetic
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006332 Cardiomegaly Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES. Cardiac Hypertrophy,Enlarged Heart,Heart Hypertrophy,Heart Enlargement,Cardiac Hypertrophies,Enlargement, Heart,Heart Hypertrophies,Heart, Enlarged,Hypertrophies, Cardiac,Hypertrophies, Heart,Hypertrophy, Cardiac,Hypertrophy, Heart
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
Species specificity of renin kinetics in transgenic rats harboring the human renin and angiotensinogen genes.
August 1992, Proceedings of the National Academy of Sciences of the United States of America,
Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
Pressure-natriuresis and -diuresis in transgenic rats harboring both human renin and human angiotensinogen genes.
December 1998, Journal of the American Society of Nephrology : JASN,
Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
Cyclosporin A protects against angiotensin II-induced end-organ damage in double transgenic rats harboring human renin and angiotensinogen genes.
January 2000, Hypertension (Dallas, Tex. : 1979),
Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
Human renin-dependent hypertension in rats transgenic for human angiotensinogen.
March 1996, Hypertension (Dallas, Tex. : 1979),
Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes.
August 2013, Clinical science (London, England : 1979),
Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
Toll-like receptor 2 signaling deficiency in cardiac cells ameliorates Ang II-induced cardiac inflammation and remodeling.
July 2021, Translational research : the journal of laboratory and clinical medicine,
Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy.
January 2012, Hypertension (Dallas, Tex. : 1979),
Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
Dose effects of human renin in rats transgenic for human angiotensinogen.
April 1997, Hypertension (Dallas, Tex. : 1979),
Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
Downregulation of miR-128 Ameliorates Ang II-Induced Cardiac Remodeling via SIRT1/PIK3R1 Multiple Targets.
January 2021, Oxidative medicine and cellular longevity,
Agnieszka Biala, and Eveliina Tauriainen, and Antti Siltanen, and Jin Shi, and Saara Merasto, and Marjut Louhelainen, and Essi Martonen, and Piet Finckenberg, and Dominik N Muller, and Eero Mervaala
A nonpeptide, piperidine renin inhibitor provides renal and cardiac protection in double-transgenic mice expressing human renin and angiotensinogen genes.
December 2008, Cardiovascular drugs and therapy,
Copied contents to your clipboard!