Long-term Pharmacological Activation of PPARγDoes not Prevent Left Ventricular Remodeling in Dogs with Advanced Heart Failure

Suzuki, George; Khanal, Sanjaya; Rastogi, Sharad; Morita, Hideaki; Mishima, Takayuki; Anagnostopoulos, Petros V.; Nass, Omar; Sharov, Victor G.; Tanhehco, Elaine J.; Goldstein, Sidney; Sabbah, Hani N.

doi:10.1007/s10557-007-6003-9

Cited by 7 publications

(4 citation statements)

References 40 publications

(36 reference statements)

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“…We found no differences in PPAR-γ mRNA and protein levels between SHAM and HF rats, as previously reported by others in dog heart tissues, 21 but PPAR-γ DNA binding activity was significantly decreased in both the PVN - the brain region we chose to examine - and in the control non-infarct region of LV in HF rats, compared with SHAM rats. Thus, the transcriptional activity of PPAR-γ, rather than the actual amount of PPAR-γ, was reduced in the PVN of HF rats.…”

Section: Discussionsupporting

confidence: 87%

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Peroxisome Proliferator-Activated Receptor-γ Regulates Inflammation and Renin-Angiotensin System Activity in the Hypothalamic Paraventricular Nucleus and Ameliorates Peripheral Manifestations of Heart Failure

Zhang

Wei

et al. 2012

Hypertension

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Activation of peroxisome proliferator-activated receptor (PPAR)-γ, a nuclear transcription factor, has been shown to inhibit the production of proinflammatory cytokines and, in peripheral tissues, to down-regulate the renin-angiotensin system (RAS). PPAR-γ is expressed in key brain areas involved in cardiovascular and autonomic regulation. We hypothesized that activation of central PPAR-γ would reduce sympathetic excitation and ameliorate peripheral manifestations of heart failure (HF) by inhibiting central inflammation and brain RAS activity. Two weeks after coronary artery ligation, HF rats received an intracerebroventricular (ICV) infusion of the PPAR-γ agonist pioglitazone or vehicle for another 2 weeks. PPAR- expression in the paraventricular nucleus of hypothalamus (PVN), an important cardiovascular region, was unchanged in HF compared with sham-operated (SHAM) rats. However, PPAR-γ DNA binding activity was reduced, nuclear factor-kB activity was increased, and expression of proinflammatory cytokines and angiotensin II type-1 receptor was augmented in the HF rats. Mean blood pressure response to ganglionic blockade was greater, plasma norepinephrine levels, lung/body weight, right ventricle/body weight, and left ventricular end-diastolic pressure were increased and maximal left ventricular dP/dt was decreased. All these findings were ameliorated in HF rats treated with ICV pioglitazone, which increased PPAR-γ expression and DNA binding activity in PVN. The results demonstrate that cardiovascular and autonomic mechanisms leading to heart failure after myocardial infarction can be modulated by activation of PPAR-γ in the brain. Central PPAR-γ may be a novel target for treatment of sympathetic excitation in myocardial infarction-induced HF.

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Section: Discussionsupporting

confidence: 87%

“…15–18 Limited studies have examined the effects of peripherally administered PPAR-γ agonists on the progression of HF, but the results have been controversial. 19–21 …”

Section: Introductionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor-γ Regulates Inflammation and Renin-Angiotensin System Activity in the Hypothalamic Paraventricular Nucleus and Ameliorates Peripheral Manifestations of Heart Failure

Zhang

Wei

et al. 2012

Hypertension

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“…43,51–54 The safety of glitazones, employed in diabetes therapy, has recently been called into question with the observation that several of the major PPARγ-activating drugs are associated with increased cardiovascular morbidity and mortality. 45,55–58 Indeed, cardiovascular and other complications linked to the use of PPARγ agonists has led to restrictions on the use of glitazones or their withdrawal from several markets.…”

Section: Metabolic Remodeling Associated With Hfmentioning

confidence: 99%

Mitochondrial Protein Phosphorylation as a Regulatory Modality: Implications for Mitochondrial Dysfunction in Heart Failure

O’Rourke¹,

Eyk²,

Foster³

2011

Congestive Heart Failure

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Phosphorylation of mitochondrial proteins has been recognized for decades, and the regulation of pyruvate- and branched-chain α-ketoacid dehydrogenases by an atypical kinase/phosphatase cascade is well established. More recently, the development of new mass spectrometry-based technologies has led to the discovery of many novel phosphorylation sites on a variety of mitochondrial targets. The evidence suggests that the major classes of kinase and several phosphatases may be present at the mitochondrial outer membrane, intermembrane space, inner membrane, and matrix, but many questions remain to be answered as to the location, timing, and reversibility of these phosphorylation events and whether they are functionally relevant. The authors review phosphorylation as a mitochondrial regulatory strategy and highlight its possible role in the pathophysiology of cardiac hypertrophy and failure.

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“…During the 2000s, the experimental studies that tested in dogs the efficacy of drugs used for CHF in humans (DMH) were fewer than in the previous decades [ 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 ]. In contrast, there was an increase in studies published in veterinary medicine journals that evaluated the...…”

Section: Resultsmentioning

confidence: 99%

Management of Chronic Congestive Heart Failure Caused by Myxomatous Mitral Valve Disease in Dogs: A Narrative Review from 1970 to 2020

Bagardi

Zamboni

Locatelli

et al. 2022

Animals

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The treatment of chronic congestive heart failure (CHF), secondary to myxomatous mitral valve disease (MMVD) in dogs, has considerably changed in the last fifty years. An analysis of the literature concerning the therapy of chronic CHF in dogs affected by MMVD is not available, and it is needed. Narrative reviews (NRs) are aimed at identifying and summarizing what has been previously published, avoiding duplications, and seeking new study areas that have not yet been addressed. The most accessible open-access databases, PubMed, Embase, and Google Scholar, were chosen, and the searching time frame was set in five decades, from 1970 to 2020. The 384 selected studies were classified into categories depending on the aim of the study, the population target, the pathogenesis of MMVD (natural/induced), and the resulting CHF. Over the years, the types of studies have increased considerably in veterinary medicine. In particular, there have been 43 (24.29%) clinical trials, 41 (23.16%) randomized controlled trials, 10 (5.65%) cross-over trials, 40 (22.60%) reviews, 5 (2.82%) comparative studies, 17 (9.60%) case-control studies, 2 (1.13%) cohort studies, 2 (1.13%) experimental studies, 2 (1.13%) questionnaires, 6 (3.40%) case-reports, 7 (3.95%) retrospective studies, and 2 (1.13%) guidelines. The experimental studies on dogs with an induced form of the disease were less numerous (49–27.68%) than the studies on dogs affected by spontaneous MMVD (128–72.32%). The therapy of chronic CHF in dogs has considerably changed in the last fifty years: in the last century, some of the currently prescribed drugs did not exist yet, while others had different indications.

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Long-term Pharmacological Activation of PPARγDoes not Prevent Left Ventricular Remodeling in Dogs with Advanced Heart Failure

Abstract: Long-term PPARgamma activation with GW did not prevent progressive LV remodeling in dogs with advanced heart failure.

Cited by 7 publications

References 40 publications

Peroxisome Proliferator-Activated Receptor-γ Regulates Inflammation and Renin-Angiotensin System Activity in the Hypothalamic Paraventricular Nucleus and Ameliorates Peripheral Manifestations of Heart Failure

Peroxisome Proliferator-Activated Receptor-γ Regulates Inflammation and Renin-Angiotensin System Activity in the Hypothalamic Paraventricular Nucleus and Ameliorates Peripheral Manifestations of Heart Failure

Mitochondrial Protein Phosphorylation as a Regulatory Modality: Implications for Mitochondrial Dysfunction in Heart Failure

Management of Chronic Congestive Heart Failure Caused by Myxomatous Mitral Valve Disease in Dogs: A Narrative Review from 1970 to 2020

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