Inhibition of TGF-β prevents cardiac fibrosis and diastolic dysfunction in hypertensive rats

1999 ◽  
Vol 5 (3) ◽  
pp. 77
Author(s):  
Fumitaka Kuwahara ◽  
Hisashi Kai ◽  
Tsuyoshi Nagata ◽  
Rei Shibata ◽  
Hiroshi Niiyama ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Cardiac Fibrosis ◽  
Hypertensive Rats

scholarly journals Chronic, low-dose TMAO treatment reduces diastolic dysfunction and heart fibrosis in hypertensive rats

2018 ◽  
Vol 315 (6) ◽  
pp. H1805-H1820 ◽  
Author(s):  
Tomasz Huc ◽  
Adrian Drapala ◽  
Marta Gawrys ◽  
Marek Konop ◽  
Klaudia Bielinska ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Natriuretic Peptide ◽  
Cardiac Fibrosis ◽  
Diastolic Pressure ◽  
Circulatory System ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Negative Effects ◽  
Lower Plasma ◽  
Trimethylamine Oxide

Several studies have suggested negative effects of trimethylamine oxide (TMAO) on the circulatory system. However, a number of studies have shown protective functions of TMAO, a piezolyte and osmolyte, in animals exposed to high hydrostatic and/or osmotic stress. We evaluated the effects of TMAO treatment on the development of hypertension and its complications in male spontaneously hypertensive rats (SHRs) maintained on water (SHR-Water) and SHRs drinking TMAO water solution from weaning (SHR-TMAO). Wistar-Kyoto (WKY) rats were used as normotensive controls to discriminate between age-dependent and hypertension-dependent changes. Telemetry measurements of blood pressure were performed in rats between the 7th and 16th weeks of life. Anesthetized rats underwent echocardiographic, electrocardiographic, and direct left ventricular end-diastolic pressure (LVEDP) measurements. Hematoxylin and eosin as well as van Gieson staining for histopathological evaluation were performed. Plasma TMAO measured by chromatography coupled with mass spectrometry was significantly higher in the SHR-Water group compared with the WKY group (~20%). TMAO treatment increased plasma TMAO by four- to fivefold and did not affect the development of hypertension in SHRs. Sixteen-week-old rats in the SHR-Water and SHR-TMAO groups (12-wk TMAO treatment) showed similar blood pressures, angiopathy, and cardiac hypertrophy. However, the SHR-TMAO group had lower plasma NH2-terminal pro-B-type natriuretic peptide, LVEDP, and cardiac fibrosis. In contrast to age-matched WKY rats, 60-wk-old SHRs showed hypertensive angiopathy and heart failure with preserved ejection fraction. Compared with the SHR-Water group, the SHR-TMAO group (56-wk TMAO treatment) showed significantly lower plasma NH2-terminal pro-B-type natriuretic peptide and vasopressin, significantly lower LVEDP, and cardiac fibrosis. In conclusion, a four- to fivefold increase in plasma TMAO does not exert negative effects on the circulatory system. In contrast, increased dietary TMAO seems to reduce diastolic dysfunction in pressure-overloaded hearts in rats. NEW & NOTEWORTHY Chronic, low-dose trimethylamine oxide (TMAO) treatment that increases plasma TMAO by four- to fivefold reduces plasma NH2-terminal pro-B-type natriuretic peptide and vasopressin, left ventricular end-diastolic pressure, and cardiac fibrosis in pressure-overloaded hearts in hypertensive rats. Our study provides evidence that a moderate increase in plasma TMAO does not have a negative effect on the circulatory system. In contrast, increased dietary TMAO seems to reduce diastolic dysfunction in the pressure-overloaded heart.

Kidney-Heart Connection: Experimental Mild Renal Insufficiency Induces Early Cardiac Fibrosis and Myocardial Diastolic Dysfunction Followed by Late Systolic Failure

2008 ◽  
Vol 14 (6) ◽  
pp. S17
Author(s):  
Fernando L. Martin ◽  
Josef Korinek ◽  
Brenda K. Huntley ◽  
Elise A. Oehler ◽  
Gerald E. Harders ◽  
...  
Keyword(s):  
Renal Insufficiency ◽  
Diastolic Dysfunction ◽  
Cardiac Fibrosis ◽  
Mild Renal Insufficiency

scholarly journals A Polyphenol Rich Muscadine Grape Extract Reduces Macrophage Infiltration in Hypertensive Rat Hearts Associated with a Reduction in Macrophage Migration

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 52-52
Author(s):  
Ana Clara Melo ◽  
Pooja Patil ◽  
Patricia Gallagher ◽  
Elisabeth Tallant
Keyword(s):  
Blood Pressure ◽  
Inflammatory Response ◽  
Diastolic Dysfunction ◽  
Cardiac Fibrosis ◽  
Total Phenolics ◽  
Ang Ii ◽  
Water Control ◽  
Grape Extract ◽  
Collagen Iii ◽  
Muscadine Grape

Abstract Objectives Hypertension affects over a billion people world-wide and is a major risk factor for cardiovascular disease. Macrophages, the most abundant innate immune cells, home to the heart and secrete cytokines, inducing a heightened inflammatory response which results in fibrosis and cardiac damage. Muscadine grapes are rich in polyphenols, compounds with anti-proliferative, anti-fibrotic, and anti-inflammatory properties. Our aim was to determine whether a muscadine grape extract (MGE) rich in polyphenols prevents the macrophage inflammatory response induced by hypertension. Methods A proprietary extract was prepared from muscadine grape seeds and skins. Male Sprague-Dawley rats (8 weeks old) received drinking water (control), MGE at 0.2 mg total phenolics/mL, 24 μg/kg/h of angiotensin II (Ang II) via osmotic minipump to induce hypertension, or both Ang II and MGE (Ang II/MGE) for 4 weeks. Rats were pre-treated with MGE for 1 week prior to Ang II treatment. Blood pressure was measured weekly by tail cuff plethysmography. Tissues were collected and fixed for immunohistochemistry. Proliferation and migration of macrophage-like RAW264.7 cells were quantified in real-time. Results MGE had no effect on blood pressure in normotensive or hypertensive rats. MGE ameliorated Ang II-induced diastolic dysfunction (E/E’ ratio: 19.9 ± 0.8 control, 28.1 ± 1.1 Ang II, 22.3 ± 2.0 Ang II/MGE rats; n = 8; P < 0.05), interstitial cardiac fibrosis (P < 0.05) and collagen III deposition (0.9 ± 0.2% Control, 6.8 ± 1.0% Ang II, 2.8 ± 0.4% Ang II/MGE; P < 0.01). Thus, MGE may improve diastolic dysfunction in part through a reduction in pathological fibrosis. Ang II caused a significant increase in CD68-positive macrophages in cardiac tissue, which was blocked by MGE (% positive cells/field: control 6.1 ± 0.4, Ang II 12.5 ± 2.0, Ang II/MGE 5.4 ± 0.5, P < 0.01). Treatment of RAW264.6 cells with MGE (20 μg/mL total phenolics) for 18 h attenuated stimulated cell migration by 2-fold with no effect on proliferation (n = 3, P < 0.5), indicating that MGE may reduce the Ang II-mediated increase in cardiac macrophages by blocking migration. Conclusions MGE may serve as medical food to protect the heart from hypertension-induced inflammation thereby reducing cardiac fibrosis to improve diastolic dysfunction. Funding Sources Chronic Disease Research Fund.

scholarly journals Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA-salt hypertensive rats

2002 ◽  
Vol 135 (4) ◽  
pp. 961-968 ◽  
Author(s):  
Stevo Mirkovic ◽  
Anne-Marie L Seymour ◽  
Andrew Fenning ◽  
Anna Strachan ◽  
Solomon B Margolin ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Hypertensive Rats
Sign in / Sign up

Export Citation Format

Share Document