Search

Your search keyword '"Y.S. Prakash"' showing total 61 results
Start Over Author "Y.S. Prakash"
61 results on '"Y.S. Prakash"'

1. Kisspeptins inhibit human airway smooth muscle proliferation

Author

Niyati A. Borkar, Nilesh Sudhakar Ambhore, Rama Satyanarayana Raju Kalidhindi, Christina M. Pabelick, Y.S. Prakash, and Venkatachalem Sathish

Subjects
Muscle biology, Pulmonology, Medicine
Abstract

Sex and gender disparity in asthma is recognized and suggests a modulatory role for sex steroids, particularly estrogen. However, there is a dichotomous role for estrogen in airway remodeling, making it unclear whether sex hormones are protective or detrimental in asthma and suggesting a need to explore mechanisms upstream or independent of estrogen. We hypothesize that kisspeptin (Kp)/KISS1R signaling serves this role. Airway smooth muscle (ASM) is a key structural cell type that contributes to remodeling in asthma. We explored the role of Kp/KISS1R in regulating ASM proliferation. We report potentially novel data indicating that Kp and KISS1R are expressed in human airways, especially ASM, with lower expression in ASM from women compared with men and lower in patients with asthma compared with people without asthma. Proliferation studies showed that cleaved forms of Kp, particularly Kp-10, mitigated PDGF-induced ASM proliferation. Pharmacological inhibition and shRNA knockdown of KISS1R increased basal ASM proliferation, which was further amplified by PDGF. The antiproliferative effect of Kp-10 in ASM was mediated by inhibition of MAPK/ERK/Akt pathways, with altered expression of PCNA, C/EBP-α, Ki-67, cyclin D1, and cyclin E leading to cell cycle arrest at G0/G1 phase. Overall, we demonstrate the importance of Kp/KISS1R signaling in regulating ASM proliferation and a potential therapeutic avenue to blunt remodeling in asthma.

Published
2022
Full Text
View/download PDF

3. Cigarette Smoke and Estrogen Signaling in Human Airway Smooth Muscle

Author

Venkatachalem Sathish, Michelle R. Freeman, Emma Long, Michael A. Thompson, Christina M. Pabelick, and Y.S. Prakash

Subjects
Store operated calcium entry, Bronchodilation, Bronchoconstriction, Estrogen Receptor, Calcium Regulation, STIM1, Sex Steroid, Lung, Secondhand Smoke, Physiology, QP1-981, Biochemistry, QD415-436
Abstract

Aims: Cigarette smoke (CS) in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective) bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE) on 17β-estradiol (E2) signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM) obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca2+]i) responses to 10µM histamine. Acute exposure to physiological concentrations of E2 decreased [Ca2+]i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E2 on [Ca2+]i was blunted. Acute E2 exposure also decreased store-operated Ca2+ entry and inhibited stromal interaction molecule 1 (STIM1) phosphorylation: effects blunted by CSE. Acute exposure to E2 increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E2 compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

Published
2015
Full Text
View/download PDF

4. Restoration of Mitochondrial Cardiolipin Attenuates Cardiac Damage in Swine Renovascular Hypertension

Author

Alfonso Eirin, Behzad Ebrahimi, Soon Hyo Kwon, Justin A. Fiala, Barbara J. Williams, John R. Woollard, Quan He, Ramech C. Gupta, Hani N. Sabbah, Y.S. Prakash, Stephen C. Textor, Amir Lerman, and Lilach O. Lerman

Subjects
bendavia, heart failure, hypertension, mitochondria, renal artery stenosis, renovascular hypertension, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundRenovascular hypertension (RVH) impairs cardiac structure and left ventricular (LV) function, but whether mitochondrial injury is implicated in RVH‐induced myocardial damage and dysfunction has not been defined. We hypothesized that cardiac remodeling in swine RVH is partly attributable to cardiac mitochondrial injury. Methods and ResultsAfter 12 weeks of hypercholesterolemic (HC)‐RVH or control (n=14 each), pigs were treated for another 4 weeks with vehicle or with the mitochondrial‐targeted peptide (MTP), Bendavia (0.1 mg/kg subcutaneously, 5 days/week), which stabilizes mitochondrial inner‐membrane cardiolipin (n=7 each). Cardiac function was subsequently assessed by multidetector‐computed tomography and oxygenation by blood‐oxygen‐level–dependent magnetic resonance imaging. Cardiolipin content, mitochondrial biogenesis, as well as sarcoplasmic‐reticulum calcium cycling, myocardial tissue injury, and coronary endothelial function were assessed ex vivo. Additionally, mitochondrial cardiolipin content, oxidative stress, and bioenergetics were assessed in rat cardiomyocytes incubated with tert‐butyl hydroperoxide (tBHP) untreated or treated with MTP. Chronic mitoprotection in vivo restored cardiolipin content and mitochondrial biogenesis. Thapsigargin‐sensitive sarcoplasmic reticulum Ca2+‐ATPase activity that declined in HC‐RVH normalized in MTP‐treated pigs. Mitoprotection also improved LV relaxation (E/A ratio) and ameliorated cardiac hypertrophy, without affecting blood pressure or systolic function. Myocardial remodeling and coronary endothelial function improved only in MTP‐treated pigs. In tBHP‐treated cardiomyocytes, mitochondrial targeting attenuated a fall in cardiolipin content and bioenergetics. ConclusionsChronic mitoprotection blunted myocardial hypertrophy, improved LV relaxation, and attenuated myocardial cellular and microvascular remodeling, despite sustained HC‐RVH, suggesting that mitochondrial injury partly contributes to hypertensive cardiomyopathy.

Published
2016
Full Text
View/download PDF

5. Activation of PIEZO1 Inhibits Kidney Cystogenesis

Author

Fan, Qingfeng, primary, Hadla, Mohamad, additional, Peterson, Zack, additional, Nelson, Grace, additional, Ye, Hong, additional, Wang, Xiaofang, additional, Mardirossian, Jea-Marc, additional, Harris, Peter C., additional, Alper, Seth L, additional, Y.S., Prakash, additional, Beyder, Arthur, additional, Torres, Vicente E., additional, and Chebib, Fouad T., additional

Published
2024
Full Text
View/download PDF

6. Age-associated differences in the human lung extracellular matrix

Author

M.L. Koloko Ngassie, M. De Vries, T. Borghuis, W. Timens, Don D. Sin, D. Nickle, P. Joubert, P. Horvatovich, G. Marko-Varga, J.J. Teske, J.M. Vonk, R. Gosens, Y.S. Prakash, J.K. Burgess, and C.A. Brandsma

Subjects
Pulmonary and Respiratory Medicine, Adult, Proteomics, Adolescent, Physiology, Lung Diseases/metabolism, Cell Biology, Extracellular Matrix/metabolism, Lung/metabolism, Middle Aged, Extracellular Matrix Proteins/genetics, Young Adult, Physiology (medical), 80 and over, Humans, Aged
Abstract

IntroductionExtracellular matrix (ECM) remodelling has been associated with chronic lung diseases. However, information about specific age-associated differences in lung ECM is currently limited. In this study we aimed to identify and localize age-associated ECM differences in human lung using comprehensive transcriptomic, proteomic and immunohistochemical analyses.MethodsOur previously identified age-associated gene expression signature of the lung was re-analysed limiting it to an aging signature based on 270 control patients (37-80 years) and focused on the Matrisome core geneset using geneset enrichment analysis. To validate the age-associated transcriptomic differences on protein level, we compared the age-associated ECM genes (F ResultsComparative analysis of transcriptomic and proteomic data identified 7 ECM proteins with higher expression with age at both gene and protein level: COL1A1, COL6A1, COL6A2, COL14A1, FBLN2, LTBP4 and LUM. With immunohistochemistry we demonstrated higher protein expression with age for COL6A2 in whole tissue, parenchyma, airway wall and blood vessel, for COL14A1 in bronchial epithelium and blood vessel, and for FBLN2 and COL1A1 in lung parenchyma.ConclusionOur study revealed that higher age is associated with lung ECM remodelling, with specific differences occurring in defined regions within the lung. These differences may affect lung structure and physiology with aging and as such may increase susceptibility for developing chronic lung diseases.Key messagesWhat is already known on this topicsummarise the state of scientific knowledge on this subject before you did your study and why this study needed to be done.❖ In animal models, it has been demonstrated that aging alters the composition of the lung ECM, with more deposition of collagen and degradation of elastin. Similar ECM differences have been observed in age-associated chronic lung diseases, including COPD; moreover, we observed in lung tissue that several ECM genes associate differently with age in COPD patients compared to non-COPD controls(1). Detailed knowledge on age-associated changes in specific ECM proteins as well as regional differences within the lung is lacking.What this study addssummarise what we now know as a result of this study that we did not know before.❖ We identified 7 age-associated ECM proteins i.e. COL1A1, COL6A1, COL6A2 COL14A1, FBLN2, LTBP4 and LUM with higher transcript and protein levels in human lung tissue with age. Extensive immunohistochemical analysis revealed significant age-associated differences for 3 of these ECM proteins in specific compartments of the lung, with the most notable differences in the blood vessels and parenchyma.How this study might affect research, practice, or policysummarise the implications of this study.❖ The identification of age-associated differences in specific human lung ECM proteins lays a new foundation for the investigation of ECM differences in age-associated chronic lung diseases. Additionally, examining the function of these age-associated ECM proteins and their cellular interactions in lung injury and repair responses may provide novel insight in mechanisms underlying chronic lung diseases.

Published
2023

17. Cellular senescence is associated with trisomies during human lung development

Author

Randa Belgacemi, Caroline Cherry, Ian Glass, Gail Deutsch, Y.S Prakash, Christina Pabelick, Soula Danopoulos, and Denise Al Alam

Subjects
Physiology
Abstract

Rationale Human chromosomal anomalies, notably trisomies, induce several alterations in gene expression, leading to various disease phenotypes. Recent studies showed that dermal fibroblasts from patients with trisomy 13 (T13), T18 or T21 present features of increased senescence and oxidative stress. We recently demonstrated that T21 lungs present abnormalities prenatally. Senescence is a state of cell division arrest that plays an important role in organogenesis. However, little is known about cellular senescence in fetal human lung with T13, T18 and T21. We therefore sought to characterize cellular senescence in these lung tissues. Methods Fresh human fetal lung tissues with T13, T18 and T21 were collected along with euploid age and sex matched controls. RT-qPCR and immunofluorescence staining (IF) were performed to assess the expression of senescence markers as well as Senescence-Associated Secretory Phenotype (SASP) elements in the various lung compartments (epithelial and mesenchymal). In addition, fibroblasts were isolated and cultured from each sample to determine the extent of senescence on isolated mesenchyme by IF and RT-qPCR. Staining for oxidative stress detection and Reactive oxygen species were assessed by CellROX and MitoSOX. Results RT-qPCR analysis in T13 whole lung tissues demonstrated no significant differences in the expression of either senescence or SASP markers as compared to control ( P16/ P21/ TP53 and IL6/ IL1 β/ TGF β/ CXCL8 respectively; n=5). Interestingly however, IF staining in T13 tissues showed a significant increase of γ-H2AFX, a marker of senescence, in the mesenchyme (n=4) as well as significantly decreased P21 staining in both the epithelial and mesenchymal compartments. Additionally, isolated fibroblasts from T13 lungs expressed significantly more IL6 as compared to control (n=3), with IF staining demonstrating a significant increase of γ-H2AFX. T18 lungs displayed significantly increased expression of P16 as compared to control (n=6), whereas IF staining revealed an increase of γ-H2AFX in whole tissue (n=4). Fibroblasts isolated from T18 lungs revealed no significant difference in any markers (gene or protein). Lastly, T21 lungs showed a significant increase of CXCL8 expression as compared to control (n=6). IF staining of T21 lungs demonstrated an increase γ-H2AFX in both the epithelium and mesenchyme (n=8). However, isolated T21 lung fibroblasts displayed significantly increased expression of P16, P21, TP53, and CXCL8. Furthermore, IF staining of T21 lung fibroblasts displayed significantly more γ-H2AFX and P21 positive cells as compared to controls (n=5). Interestingly, only cells from T21 lungs presented a significant increase of CellROX and MitoSOX staining (n=5). Conclusion In this study we established that expression of both senescence and SASP markers differ depending on the trisomy. Our results suggest that cellular senescence is more pronounced in lungs from individuals with trisomy 21. These authors acknowledge funding from NIH/NHLBI R01HL141856 (to DAA); NIH/ Office Of The Director, National Institutes Of Health (OD) R01HL155104 (SD); NIH/NHLBI R21HL165411 (SD and DAA); CIRM training grant EDUC4-12837 (RB) and NIH/NICHD 2R24HD000836-52 (IG). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Published
2023

28. Hormonal Effects on Asthma, Rhinitis, and Eczema

Author

Natalia Weare-Regales, Sergio E. Chiarella, Juan Carlos Cardet, Y.S. Prakash, and Richard F. Lockey

Subjects
Diabetes Mellitus, Type 2, Eczema, Prevalence, Immunology and Allergy, Humans, Asthma, Dermatitis, Atopic, Rhinitis
Abstract

Hormones significantly influence the pathogenesis of asthma, rhinitis, and eczema. This review aims to summarize relevant clinical considerations for practicing allergists and immunologists. The first section reviews the effects of sex hormones: estrogen, progesterone, and testosterone. The second concerns insulin production in the context of type 1 and type 2 diabetes. The third concludes with a discussion of thyroid and adrenal pathology in relationship to asthma, rhinitis, and eczema.

Published
2021

44. Collaboration, Advocacy, and the ARC

Author

Y.S. Prakash, Lee A. Fleisher, Max B. Kelz, and James C. Eisenach

Subjects
Arc (geometry), business.industry, General Engineering, General Earth and Planetary Sciences, Aerospace engineering, business, Geology, General Environmental Science
Published
2021

45. Contributors

Author

Anurag Agrawal, Maryellen C. Antkowiak, Melinda A. Beck, Sapna Bhatia, Ellen E. Blaak, Richard N. Channick, David Chapman, Rituparna Chaudhuri, Veronica De Rosa, Anne E. Dixon, Debbie M. Figueroa, Erick Forno, Gijs H. Goossens, Elizabeth M. Gordon, William D. Green, Chenjuan Gu, Richard A. Johnston, Jonathan C. Jun, Erik A. Karlsson, Gregory King, Stewart J. Levine, Benjamin J. Marsland, Giuseppe Matarese, J. Justin Milner, Christina Pabelick, Francesco Perna, Vsevolod Y. Polotsky, Y.S. Prakash, Claudio Procaccini, Deepa Rastogi, Aman Rathore, Jennifer Rebeles, Stacey Schultz-Cherry, Stephanie A. Shore, Akshay Sood, Renee D. Stapleton, Benjamin T. Suratt, Michael A. Thompson, Niki D.J. Ubags, Rens L.J. van Meijel, Xianglan Yao, and Haris Younas

Published
2019

46. The Effect of Continuous Positive Airway Pressure in a Mouse Model of Hyperoxic Neonatal Lung Injury

Author

Brent Reyburn, Thomas M. Raffay, Juliann M. Di Fiore, Richard J. Martin, Y.S. Prakash, Anjum Jafri, and Peter M. MacFarlane

Subjects
musculoskeletal diseases, Hyperoxia, Pulmonary mechanics, Supplemental oxygen, business.industry, medicine.medical_treatment, Lung injury, medicine.disease, Respiratory support, respiratory tract diseases, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Bronchopulmonary dysplasia, 030225 pediatrics, Anesthesia, Pediatrics, Perinatology and Child Health, medicine, Continuous positive airway pressure, medicine.symptom, Neonatal lung, business, Developmental Biology
Abstract

Background: Continuous positive airway pressure (CPAP) and supplemental oxygen have become the mainstay of neonatal respiratory support in preterm infants. Although oxygen therapy is associated with respiratory morbidities including bronchopulmonary dysplasia (BPD), the long-term effects of CPAP on lung function are largely unknown. We used a hyperoxia-induced mouse model of BPD to explore the effects of daily CPAP in the first week of life on later respiratory system mechanics. Objective: We wanted to test the hypothesis that daily CPAP in a newborn-mouse model of BPD improves longer-term respiratory mechanics. Methods: Mouse pups from C57BL/6 pregnant dams were exposed to room air (RA) or hyperoxia (50% O2, 24 h/day) for the first postnatal week with or without exposure to daily CPAP (6 cm H2O, 3 h/day). Respiratory system resistance (Rrs) and compliance (Crs) were measured following a subsequent 2-week period of RA recovery. Additional measurements included radial alveolar and macrophage counts. Results: Mice exposed to hyperoxia had significantly elevated Rrs, decreased Crs, reduced alveolarization and increased macrophage counts at 3 weeks when compared to RA-treated mice. Daily CPAP treatment significantly improved Rrs, Crs and alveolarization and decreased lung macrophage infiltration in the hyperoxia-exposed pups. Conclusions: We have demonstrated that daily CPAP had a longer-term benefit on baseline respiratory system mechanics in a neonatal mouse model of BPD. We speculate that this beneficial effect of CPAP was the consequence of a decrease in the inflammatory response and resultant alveolar injury associated with hyperoxic lung injury in newborns.

Published
2015

48. Contributors

Author

Soraya Abbasi, James Abbey, N. Scott Adzick, Sun-Young Ahn, Kurt H. Albertine, Karel Allegaert, Seth L. Alper, Gabriel Altit, Steven M. Altschuler, Ruben E. Alvaro, Jennifer M.H. Amorosa, Kelsey L. Anbuhl, Claus Yding Andersen, Richard A. Anderson, David J. Askenazi, Richard Lambert Auten, Julie Autmizguine, Timur Azhibekov, Stephen A. Back, Jérôme Badaut, Peter Russell Baker, Philip L. Ballard, Eduardo H. Bancalari, Tatiana Barichello, Frederick Battaglia, Michel Baum, Simon Beggs, Edward F. Bell, Corinne Benchimol, Manon J.N.L. Benders, Laura Bennet, Phillip R. Bennett, Melvin Berger, Wolfgang Bernhard, John F. Bertram, Vikrant K. Bhosle, Vinod K. Bhutani, M. Jane Black, Joseph M. Bliss, David L. Bolender, Joline E. Brandenburg, Delma L. Broussard, Laura Davidson Brown, Douglas G. Burrin, Barbara Cannon, Michael Caplan, Susan E. Carlson, David P. Carlton, Georgina Caruana, William J. Cashore, Piya Chaemsaithong, Noppadol Chaiyasit, Jennifer R. Charlton, Carol L. Cheatham, Sylvain Chemtob, Yi-Yung Chen, Robert L. Chevalier, Sadhana Chheda, Andrew J. Childs, Robert D. Christensen, Alison Chu, David H. Chu, Maria Roberta Cilio, David A. Clark, Jane Cleary-Goldman, Ethel G. Clemente, John A. Clements, Ronald I. Clyman, Susan S. Cohen, John Colombo, Richard M. Cowett, Peter A. Crawford, James E. Crowe, Luise A. Cullen-McEwen, Wayne S. Cutfield, Mary E. D'Alton, Enrico Danzer, Christophe Delacourt, Sherin U. Devaskar, Thomas G. Diacovo, Nikolina Docheva, John P. Dormans, Kevin Dysart, Afif El-Khuffash, Peter James Ellis, Kerry McGarr Empey, Baris Ercal, Melinda Erdős, Robert P. Erickson, Mohamed A. Fahim, Arij Faksh, Hans-Georg Frank, Philippe S. Friedlich, Jed Friedman, Yuansheng Gao, Marianne Garland, Donna Geddes, Michael K. Georgieff, Jason Gien, Dino A. Giussani, Armond S. Goldman, Efrén González, Misty Good, Denis M. Grant, Lucy R. Green, Emmanouil Grigoriou, Adda Grimberg, Ian Gross, Ruth E. Grunau, Jean-Pierre Guignard, Alistair Jan Gunn, Nursen Gurtunca, Alice Hadchouel, Gabriel G. Haddad, Henrik Hagberg, Thomas Hale, K. Michael Hambidge, Cathy Hammerman, Thor Willy Ruud Hansen, Mark A. Hanson, Richard Harding, Mary Catherine Harris, Peter Hartmann, Foteini Hassiotou, Guttorm Haugen, Colin P. Hawkes, William W. Hay, Christina E. Hayward, Vivi M. Heine, Ann Hellström, Michael A. Helmrath, Karen D. Hendricks-Muñoz, Emilio Herrera, Michael J. Hiatt, Steven B. Hoath, Stuart B. Hooper, Stephen A. Huang, Silvia Iacobellli, Terrie E. Inder, M. Luisa Iruela-Arispe, Sudarshan R. Jadcherla, Deepak Jain, Thomas Jansson, John Lynn Jefferies, Jennifer G. Jetton, Alan H. Jobe, Lois H. Johnson, Richard B. Johnston, Rebecca Lee Jones, Pedro A. Jose, Satish C. Kalhan, Suhas G. Kallapur, Michael Kaplan, Stanley Kaplan, Heidi Eigenrauch Karpen, Saul J. Karpen, S. Ananth Karumanchi, Frederick J. Kaskel, Anup C. Katheria, Lorraine E. Levitt Katz, Susan E. Keeney, Steven E. Kern, Shirin Khanjani, Laurie E. Kilpatrick, Chang-Ryul Kim, John P. Kinsella, Torvid Kiserud, Joyce M. Koenig, Tobias R. Kollmann, Jay K. Kolls, Nancy F. Krebs, Thomas J. Kulik, Jessica Katz Kutikov, Satyan Lakshminrusimha, Angelo A. Lamola, Miguel Angel Lasunción, Pascal M. Lavoie, Tucker W. LeBien, Mary M. Lee, Matthew K. Lee, Yvonne K. Lee, Sandra Leibel, Fred Levine, Ofer Levy, Yang Liu, Steven Lobritto, Cynthia A. Loomis, Colleen A. Lopez, David A. MacIntyre, Maxime M. Mahe, Akhil Maheshwari, Anastasiya Mankouski, Carlos B. Mantilla, Arnaud Marchant, Kara Gross Margolis, M. Michele Mariscalco, László Maródi, Karel Maršál, Richard J. Martin, Douglas G. Matsell, Dwight E. Matthews, Harry J. McArdle, James L. McManaman, Patrick J. McNamara, Patrick S. McQuillen, Tim C. McQuinn, Judith S. Mercer, Giacomo Meschia, Steven P. Miller, Parviz Minoo, Paul Monagle, Jacopo P. Mortola, Louis J. Muglia, Upender K. Munshi, Ran Namgung, Sumana Narasimhan, Jan Nedergaard, Josef Neu, Sanjay K. Nigam, Lawrence M. Nogee, Shahab Noori, Barbara M. O'Brien, Robin K. Ohls, Henar Ortega-Senovilla, Justin M. O'Sullivan, Sarah A. Owusu, Abhijeet Pal, Howard B. Panitch, Anna A. Penn, Raymond B. Penn, Cameron Pernia, Anthony F. Philipps, Joseph A. Picoraro, Francesco Pisani, David Pleasure, Jeanette R. Pleasure, Samuel J. Pleasure, Scott L. Pomeroy, Martin Post, Y.S. Prakash, Joshua D. Prozialeck, Theodore J. Pysher, Raymond Quigley, Marlene Rabinovitch, Thomas M. Raffay, J. Usha Raj, Haley Ramsey, Sarosh Rana, Tara Marie Randis, Manon Ranger, Adam J. Ratner, Timothy R.H. Regnault, Henrique Rigatto, Natalie E. Rintoul, Roberto Romero, James C. Rose, Charles R. Rosenfeld, A. Catharine Ross, Henry J. Rozycki, Thomas D. Ryan, Rakesh Sahni, Eniko Sajti, Harvey B. Sarnat, Lisa M. Satlin, Ola Didrik Saugstad, William Schierding, Frank C. Schmalstieg, George J. Schwartz, Jeffrey Schwartz, Jeffrey L. Segar, David T. Selewski, Istvan Seri, Thomas H. Shaffer, Kara N. Shah, Martin J. Shearer, Sharareh Shojaie, Noah F. Shroyer, Colin P. Sibley, Gary C. Sieck, Rebecca A. Simmons, Emidio M. Sivieri, Francine G. Smith, Lois E.H. Smith, Ian M. Smyth, Brian S. Snarr, Evan Y. Snyder, Martha Sola-Visner, Michael J. Solhaug, Mark A. Sperling, Lakshmi Srinivasan, Andreas Stahl, Charles A. Stanley, Robin H. Steinhorn, Barbara S. Stonestreet, Janette F. Strasburger, Dennis M. Styne, Lori Sussel, Emily W.Y. Tam, Libo Tan, Claire Thornton, Daniel J. Tollin, Beáta Tóth, Jeffrey A. Towbin, Ashley Trocle, William E. Truog, Reginald C. Tsang, Kristin M. Uhler, John N. Van Den Anker, Johannes (Hans) B. van Goudoever, Susan J. Vannucci, Mark H. Vickers, Daniela Virgintino, Joseph J. Volpe, Neeta L. Vora, Neha V. Vyas, Annette Wacker-Gussmann, Megan J. Wallace, Brian H. Walsh, Alice M. Wang, David Warburton, Robert M. Ward, Kristi L. Watterberg, Lynne A. Werner, Barry K. Wershil, Susan E. Wert, Andy Wessels, Jeffrey A. Whitsett, Michael Wise, Matthias T. Wolf, Marla R. Wolfson, Hector R. Wong, James L. Wynn, Lami Yeo, Stephen Yip, Bradley A Yoder, Mervin C. Yoder, Momoko Yoshimoto, Christopher J. Yuskaitis, Dan Zhou, and Ann Zovein

Published
2017

49. Restoration of Mitochondrial Cardiolipin Attenuates Cardiac Damage in Swine Renovascular Hypertension

Author

Quan He, Hani N. Sabbah, Stephen C. Textor, John R. Woollard, Amir Lerman, Soon Hyo Kwon, Behzad Ebrahimi, Justin A. Fiala, Y.S. Prakash, Ramech C. Gupta, Lilach O. Lerman, Barbara J. Williams, and Alfonso Eirin

Subjects
0301 basic medicine, Mitochondrial Diseases, renovascular hypertension, Cardiorenal Syndrome, Swine, Sus scrofa, heart failure, Apoptosis, 030204 cardiovascular system & hematology, Mitochondrion, Renal artery stenosis, Antioxidants, Mitochondria, Heart, Renovascular hypertension, Random Allocation, Ventricular Dysfunction, Left, chemistry.chemical_compound, bendavia, 0302 clinical medicine, tert-Butylhydroperoxide, Cardiolipin, Enzyme Inhibitors, Original Research, Ventricular Remodeling, mitochondria, Hypertension, Renovascular, Hypertension, Cardiology, Female, Cardiomyopathies, Cardiology and Cardiovascular Medicine, Oligopeptides, medicine.medical_specialty, Cardiolipins, Renal Artery Obstruction, Sarcoplasmic Reticulum Calcium-Transporting ATPases, 03 medical and health sciences, Internal medicine, Multidetector Computed Tomography, medicine, Animals, Ventricular remodeling, renal artery stenosis, business.industry, Atherosclerosis, medicine.disease, Disease Models, Animal, 030104 developmental biology, Endocrinology, Animal Models of Human Disease, chemistry, Heart failure, Microvessels, business, Magnetic Resonance Angiography
Abstract

BackgroundRenovascular hypertension (RVH) impairs cardiac structure and left ventricular (LV) function, but whether mitochondrial injury is implicated inRVH‐induced myocardial damage and dysfunction has not been defined. We hypothesized that cardiac remodeling in swineRVHis partly attributable to cardiac mitochondrial injury.Methods and ResultsAfter 12 weeks of hypercholesterolemic (HC)‐RVHor control (n=14 each), pigs were treated for another 4 weeks with vehicle or with the mitochondrial‐targeted peptide (MTP), Bendavia (0.1 mg/kg subcutaneously, 5 days/week), which stabilizes mitochondrial inner‐membrane cardiolipin (n=7 each). Cardiac function was subsequently assessed by multidetector‐computed tomography and oxygenation by blood‐oxygen‐level–dependent magnetic resonance imaging. Cardiolipin content, mitochondrial biogenesis, as well as sarcoplasmic‐reticulum calcium cycling, myocardial tissue injury, and coronary endothelial function were assessed ex vivo. Additionally, mitochondrial cardiolipin content, oxidative stress, and bioenergetics were assessed in rat cardiomyocytes incubated with tert‐butyl hydroperoxide (tBHP) untreated or treated withMTP. Chronic mitoprotection in vivo restored cardiolipin content and mitochondrial biogenesis. Thapsigargin‐sensitive sarcoplasmic reticulum Ca2+‐ATPase activity that declined inHC‐RVHnormalized inMTP‐treated pigs. Mitoprotection also improvedLVrelaxation (E/A ratio) and ameliorated cardiac hypertrophy, without affecting blood pressure or systolic function. Myocardial remodeling and coronary endothelial function improved only inMTP‐treated pigs. IntBHP‐treated cardiomyocytes, mitochondrial targeting attenuated a fall in cardiolipin content and bioenergetics.ConclusionsChronic mitoprotection blunted myocardial hypertrophy, improvedLVrelaxation, and attenuated myocardial cellular and microvascular remodeling, despite sustainedHC‐RVH, suggesting that mitochondrial injury partly contributes to hypertensive cardiomyopathy.

Published
2016

50. List of Contributors

Author

Allan K. Alencar, Arthur P. Arnold, Massimo Bardi, Emily J. Bartley, Jill B. Becker, Marybeth Brown, Iwona A. Buskiewicz, Carolyn M. Ecelbarger, Kelly Ethun, DeLisa Fairweather, Leanne Groban, Eric Houdeau, Sally A. Huber, Leyla Innala, Craig Kinsley, Kelly Lambert, Sarah H. Lindsey, Margaret M. McCarthy, Liana Merrill, Virginia M. Miller, Gretchen N. Neigh, Y.S. Prakash, Margarete Ribeiro-Dasilva, Venkatachalem Sathish, Peter Tiidus, Victor Viau, and Hao Wang

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results