Cardiac Remodeling and Angiotensin II-Forming Enzyme Activity of the Left Ventricle in Hamsters with Chronic Pressure Overload Induced by Ascending Aortic Stenosis

Shimizu, Miki; Tanaka, Ryou; Fukuyama, Tomoki; Aoki, Ryoko; Orito, Kensuke; Yamane, Yoshihisa

doi:10.1292/jvms.68.271

Cited by 11 publications

(7 citation statements)

References 36 publications

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“…Left ventricle hypertrophy can also be recreated by ventricular pacing in dogs [115, 118, 126], valvular stenosis in rabbits [116], and renal artery constriction or aortic stenosis in rats, hamsters, mice, rabbits and dogs [111, 119]. …”

Section: Animal Models Of Heart Failurementioning

confidence: 99%

Animal Models of Cardiovascular Diseases

Zaragoza

Gómez-Guerrero

Martin-Ventura

et al. 2011

Journal of Biomedicine and Biotechnology

304

224

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Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.

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Section: Animal Models Of Heart Failurementioning

confidence: 99%

Animal Models of Cardiovascular Diseases

Zaragoza

Gómez-Guerrero

Martin-Ventura

et al. 2011

Journal of Biomedicine and Biotechnology

304

224

View full text Add to dashboard Cite

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“…Over the past years, it has become evident that long‐term increases in angiotensin II (AII) and aldosterone (ALD) contribute to an exaggerated workload, and a progressive remodeling of the heart (i.e., cardiac fibrosis), leading to the progression of heart failure to its end stage (Cohn et al. , 2000; Shimizu et al. , 2006).…”

Section: Introductionmentioning

confidence: 99%

“…1) is one of the key neurohumoral responses to the reduced cardiac output observed in canine CHF (Watkins et al, 1976;Sayer et al, 2009). Over the past years, it has become evident that long-term increases in angiotensin II (AII) and aldosterone (ALD) contribute to an exaggerated workload, and a progressive remodeling of the heart (i.e., cardiac fibrosis), leading to the progression of heart failure to its end stage (Cohn et al, 2000;Shimizu et al, 2006). In patients with CHF, high AII and ALD concentrations have been determined as the predictors of increased mortality risk (Roig et al, 2000;Gü der et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Capturing the dynamics of systemic Renin‐Angiotensin‐Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs

Mochel

Peyrou

Fink

et al. 2012

Vet Pharm & Therapeutics

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In dogs, activation of the Renin-Angiotensin-Aldosterone System (RAAS) is an important feature of congestive heart failure (CHF). Long-term increases in angiotensin II (AII) and aldosterone (ALD) lead to the progression of heart failure to its end stage. Angiotensin-converting enzyme inhibitors (ACEIs) are the foremost therapeutic option in the management of CHF. Recent literature has challenged the efficacy of ACEIs, based on modest reduction in urinary aldosterone (UALD) excretion despite marked inhibition of ACE activity. This study was designed to heighten the understanding of the effect of benazepril, a potent ACEI, on the RAAS, using a low-sodium diet as an experimental model of RAAS activation. Time course profiles of RAAS peptides and related areas under the curve (AUC) were used for comparison between benazepril and placebo groups. Results indicated substantial changes in the dynamics of these biomarkers. At presumed benazeprilat steady state, significant differences in AUC of plasma renin activity (+90%), angiotensin I (+43%), and AII (-53%) were found between benazepril and placebo-treated dogs. ALD decreased by 73% in plasma but only by 5% in urine. In conclusion, despite modest reduction in UALD excretion, benazepril markedly influences RAAS dynamics in dogs.

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“…Hamster chymase has been used as a biological marker for the detection of various cardiovascular disorders (20), pulmonary fibrosis (21,22), and in basic fibroblast growth factor-induced angiogenesis (23). To date, however, only a very limited amount of enzymologial or other biochemical data have been published for highly purified HAM1 (24,25), and no data other than a sequence are available for HAM2.…”

mentioning

confidence: 99%

Structural Basis for Elastolytic Substrate Specificity in Rodent α-Chymases

Kervinen

Abad

Crysler

et al. 2008

Journal of Biological Chemistry

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Divergence of substrate specificity within the context of a common structural framework represents an important mechanism by which new enzyme activity naturally evolves. We present enzymological and x-ray structural data for hamster chymase-2 (HAM2) that provides a detailed explanation for the unusual hydrolytic specificity of this rodent ␣-chymase. In enzymatic characterization, hamster chymase-1 (HAM1) showed typical chymase proteolytic activity. In contrast, HAM2 exhibited atypical substrate specificity, cleaving on the carboxyl side of the P1 substrate residues Ala and Val, characteristic of elastolytic rather than chymotryptic specificity. The 2.5-Å resolution crystal structure of HAM2 complexed to the peptidyl inhibitor MeOSuc-Ala-Ala-Pro-Ala-chloromethylketone revealed a narrow and shallow S1 substrate binding pocket that accommodated only a small hydrophobic residue (e.g. Ala or Val form an easily identifiable triplet in all known rodent ␣-chymases that can be used to predict elastolytic specificity for novel chymase-like sequences. Phylogenetic comparison defines guinea pig and rabbit chymases as the closest orthologs to rodent ␣-chymases.Chymases (EC 3.4.21.39), serine proteases with a chymotrypsin-fold, are stored within the secretory granules of mast cells along with histamine, tryptases, and other inflammation mediators. When released during mast cell degranulation in various tissues, chymases participate in a variety of biological functions including regulation of vasoactive peptide processing, modulation of inflammatory response, stimulation of submucosal gland secretion, and degradation of extracellular matrix (1). Human chymase has been linked to various pathologic conditions such as allergic inflammatory reactions that can contribute to asthma (2), Crohn disease (3), inflammatory kidney disease (4), and cardiovascular disorders (5, 6).Based on the catalytic triad consisting of His, Asp, and Ser (in that order in the sequence), chymases belong to the S1A family of serine proteases that include, for example, trypsin, chymotrypsin, elastase, and cathepsin G (7, 8). Mammalian chymases divide into two phylogenetic groups, termed ␣-and ␤-chymases (9 -11). The genomes of primates, dogs, ruminants, and rodents apparently contain only one functional ␣-chymase, whereas rodents typically have several ␤-chymases. Until recently, all chymases were thought to possess chymotryptictype substrate specificity, preferring Tyr and Phe (as well as Trp and Leu, to a lesser extent) at the P1 substrate position (Schechter and Berger nomenclature (12)). However, two recent studies have clearly established elastolytic specificity (i.e. preference for small aliphatic residues Ala, Val, and Ile at the P1 position) for mouse chymase-5 (mouse mast cell protease-5; mMCP5) 4 and rat chymase-5 (rMCP5) (13,14). Neither enzyme hydrolyzed a typical chymase substrate with Phe at P1. Site-directed mutagenesis and computer modeling studies suggested Val 216 as a major contributor to this unusual substrate specificity (14).Hamster ch...

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Cardiac Remodeling and Angiotensin II-Forming Enzyme Activity of the Left Ventricle in Hamsters with Chronic Pressure Overload Induced by Ascending Aortic Stenosis

Cited by 11 publications

References 36 publications

Animal Models of Cardiovascular Diseases

Animal Models of Cardiovascular Diseases

Capturing the dynamics of systemic Renin‐Angiotensin‐Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs

Structural Basis for Elastolytic Substrate Specificity in Rodent α-Chymases

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