HMG CoA Reductase Inhibitor-Induced Myotoxicity: Pravastatin and Lovastatin Inhibit the Geranylgeranylation of Low-Molecular-Weight Proteins in Neonatal Rat Muscle Cell Culture

1997 ◽  
Vol 145 (1) ◽  
pp. 99-110 ◽  
Author(s):  
Oliver P. Flint ◽  
Barbara A. Masters ◽  
Richard E. Gregg ◽  
Stephen K. Durham
Keyword(s):  
Molecular Weight ◽  
Cell Culture ◽  
Muscle Cell ◽  
Reductase Inhibitor ◽  
Neonatal Rat ◽  
Low Molecular Weight ◽  
Rat Muscle ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase ◽  
Low Molecular Weight Proteins

Abstract 180: Synergistic Salutary Effects of HMG-CoA Reductase Inhibitor and Angiotensin II Receptor Blocker on Load-induced Heart Failure

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Yasuhiro Maejima ◽  
Mitsuaki Isobe
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Reductase Inhibitor ◽  
Neonatal Rat ◽  
Receptor Blocker ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Hmg Coa Reductase ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase

We have shown previously that combined HMG-CoA reductase inhibitor (statin) and angiotensin II receptor blocker (ARB) therapy significantly improves both symptoms and left ventricular (LV) function over time in patients with heart failure (HF) by a clinical study [ HF-COSTAR Trial]. We elucidated the mechanisms of combination therapy with the ARB (losartan, LOS) and long-acting and statin (simvastatin, SIM) for the treatment of load-induced heart failure. Salt-loaded Dahl salt-sensitive (DS) rats were treated with vehicle, LOS (5mg/kg/day), SIM (2mg/kg/day) and LOS + SIM for 16 weeks. LOS and SIM in combination improved LV dysfunction (ΔLV fractional shortening; LOS = 60%, SIM = 42%, LOS + SIM = 24%, p <0.05), limited LV hypertrophy (ΔLV septal thickness; LOS = −21%, SIM = −18%, LOS + SIM = −13%, p <0.05) and reduced cardiac fibrosis (ΔLV collagen density; LOS = −26%, SIM = −16%, LOS + SIM = −28%, p <0.05) more than LOS or SIM alone. Both Rho and matrix metalloprotease-9 (MMP-9) activity in LV tissue were increased in untreated DS rats, and LOS and SIM in combination decreased these changes more than did LOS and SIM monotherapies. We confirmed that the plasma level of Exp-3174 (E3174), a LOS metabolite and a potent inverse agonist of angiotensin II receptor type 1, was higher in rats treated with LOS and SIM in combination than in those treated with LOS alone (E3174/LOS ratio; LOS = 2.6 ± 0.3 vs. LOS + SIM = 3.2 ± 0.2, p <0.05). Next, to mimic the response of volume-overload heart failure in vitro , cultured neonatal rat cardiomyocytes (CMs) were cyclically stretched. Stretch-induced increased CM hypertrophy was suppressed by pretreatment with both SIM and E3174 more than by pretreatment with LOS, E3174, SIM, or LOS and SIM in combination. Mechanical stretch also induced activation of extracellular signal regulated kinase (ERK) and the stretch-induced ERK activation of CMs was also significantly suppressed by SIM + E3174. In conclusion, LOS and SIM had beneficial myocardial effects in rats with salt-sensitive hypertension, partly through promoting the accumulation of plasma E3174. SIM enhanced the myocardial protective effects of LOS through suppression of Rho and MMP-9 activity. Thus, a combination of ARB with statin has a promising potential as a therapeutic strategy for HF.

scholarly journals The HMG-CoA Reductase Inhibitor Activities of Soy Protein Hydrolysates from Papain Hydrolysis

Molekul ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. 145
Author(s):  
Sandra Hermanto ◽  
Aldi Octavio ◽  
Azrifitria Azrifitria ◽  
Susi Kusumaningrum
Keyword(s):  
Molecular Weight ◽  
Soy Protein ◽  
Reductase Inhibitor ◽  
Protein Hydrolysates ◽  
Molecular Weight Determination ◽  
Hmg Coa Reductase ◽  
Vitro Assay ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase ◽  
Soy Protein Hydrolysates

The search for an HMG-CoA reductase inhibitor agent as a safe and inexpensive alternative treatment for hypercholesterolemia has been carried out using soy protein hydrolysates as one of the bioactive peptide sources. This study was conducted to explore the potency of soy protein hydrolysates as an anti hypercholesterolemia agent by an in vitro assay, through the inhibition capacity of the HMG-CoA (3-hydroxy-3-methyl glutaryl-coenzyme A) reductase enzyme as a key component of cholesterol biosynthesis. Sample preparation started with soy protein isolation through acid precipitation and separated by centrifugation. The samples were analyzed the proximate content and hydrolyzed by papain enzyme at concentration 0.2% (w/v), for 0-6 hours and at 37, 50, and 55 oC. The protein hydrolysates were subsequently evaluated for hydrolysis degree (% DH), hydrolysates profile with SDS-PAGE (Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis), and anti-cholesterol assay through HMG-CoA reductase inhibition tests. The sample with the highest inhibition activity was fractionated using gel filtration chromatography (Sephadex G-10) and the molecular weight of fractions was characterized by LCMS QTOF (Liquid Chromatography-Mass Spectrometry Quadrupole Time-of-Flight) for molecular weight determination. The results indicated the optimum hydrolysis conditions of soy protein isolates were obtained at 3 hours incubation, at 50 °C with DH 33.39% and the inhibition value was 95.65% (protein concentration 39.21 μg / mL). LCMS data showed the molecular weight of fractionated peptides were 1514 and 2029 Da. We assumed that both peptides have the same affinity as previous peptides in inhibiting HMG-CoA reductase.

scholarly journals Effect of the HMG-CoA Reductase Inhibitor Simvastatin on Oxygen-Induced Retinal Neovascularization in the Neonatal Rat

2004 ◽  
Vol 16 (4) ◽  
pp. 319-327
Author(s):  
Hidetoshi ONDA ◽  
Yasuko HASEBE ◽  
Takako NAKANISHI-UEDA ◽  
Toshihiko UEDA ◽  
Shotaro KOSUGE ◽  
...  
Keyword(s):  
Reductase Inhibitor ◽  
Retinal Neovascularization ◽  
Neonatal Rat ◽  
Hmg Coa Reductase ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase

Inhibition of Copper-Associated Erythrocyte Ghost Membrane Lipid Peroxidation by Hepatic Cytosolic Low Molecular Weight Proteins

1991 ◽  
Vol 19 (3) ◽  
pp. 206-213
Author(s):  
Bruce L. Homer ◽  
Kenneth R. Pierce ◽  
Charles H. Bridges ◽  
James E. Womack ◽  
Blair A. Sowa ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Molecular Weight ◽  
Membrane Lipid ◽  
Erythrocyte Ghost ◽  
Low Molecular Weight ◽  
Membrane Lipid Peroxidation ◽  
Low Molecular Weight Proteins

Effects of an HMG-CoA reductase inhibitor, simvastatin, on human myeloma cells

2004 ◽  
Author(s):  
Takemi Otsuki ◽  
Haruko Sakaguchi ◽  
Tamayo Hatayama ◽  
Tomohiro Fujii ◽  
Takayuki Tsujioka ◽  
...  
Keyword(s):  
Reductase Inhibitor ◽  
Hmg Coa Reductase ◽  
Myeloma Cells ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase ◽  
Human Myeloma Cells
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