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2. A Novel Role of Claudin-5 in Prevention of Mitochondrial Fission Against Ischemic/Hypoxic Stress in Cardiomyocytes

Author

Luo, Tao, Liu, Haiqiong, Chen, Baihe, Liu, Han, Abdel-Latif, Ahmed, Kitakaze, Masafumi, Wang, Xianbao, Wu, Yuanzhou, Chou, Dylan, and Kim, Jin Kyung

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Cardiovascular, Heart Disease, Heart Disease - Coronary Heart Disease, Aetiology, 2.1 Biological and endogenous factors, Animals, Animals, Newborn, Apoptosis, Cells, Cultured, Claudin-5, Dynamins, GTP Phosphohydrolases, Hypoxia, Membrane Proteins, Microscopy, Electron, Transmission, Mitochondria, Heart, Mitochondrial Dynamics, Mitochondrial Proteins, Myocardial Reperfusion Injury, Myocytes, Cardiac, Rats, Rats, Sprague-Dawley, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundDownregulation of claudin-5 in the heart is associated with the end-stage heart failure. However, the underlying mechanism ofclaudin-5 is unclear. Here we investigated the molecular actions of claudin-5 in perspective of mitochondria in cardiomyocytes to better understand the role of claudin-5 in cardioprotection during ischemia.MethodsMyocardial ischemia/reperfusion (I/R; 30 min/24 h) and hypoxia/reoxygenation (H/R; 24 h/4 h) were used in this study. Confocal microscopy and transmission electron microscope (TEM) were used to observe mitochondrial morphology.ResultsClaudin-5 was detected in murine heart tissue and neonatal rat cardiomyocytes (NRCM). Its protein level was severely decreased after myocardial I/R or H/R. Confocal microscopy showedclaudin-5 presented in the mitochondria of NRCM. H/R-induced claudin-5 downregulation was accompanied by mitochondrial fragmentation. The mitofusin 2 (Mfn2) expressionwas dramatically decreased while the dynamin-related protein (Drp) 1 expression was significantly increased after H/R. The TEM indicatedH/R-induced mitochondrial swelling and fission. Adenoviral claudin-5 overexpression reversed these structural disintegration of mitochondria. The mitochondria-centered intrinsic pathway of apoptosis triggered by H/R and indicated by the cytochrome c and cleaved caspase 3 in the cytoplasm of NRCMs was also reduced by overexpressing claudin-5. Claudin-5 overexpression in mouse heart also significantly decreased cleaved caspase 3 and the infarct size in ischemic heart with improved systolic function.ConclusionWe demonstrated for the first time the presence of claudin-5 in the mitochondria in cardiomyocytes and provided the firm evidence for the cardioprotective role of claudin-5 in the preservation of mitochondrial dynamics and cell fate against hypoxia- or ischemia-induced stress.

Published
2021

4. Mitochondrial dysfunction and metabolic reprogramming induce macrophage pro-inflammatory phenotype switch and atherosclerosis progression in aging.

Author

Vendrov, Aleksandr E., Lozhkin, Andrey, Hayami, Takayuki, Levin, Julia, Fernandes Chamon, Jamille Silveira, Abdel-Latif, Ahmed, Runge, Marschall S., and Madamanchi, Nageswara R.

Subjects
METABOLIC reprogramming, METABOLIC disorders, MITOCHONDRIA, BRACHIOCEPHALIC trunk, PHENOTYPES, ATHEROSCLEROSIS, MITOCHONDRIAL pathology
Abstract

Introduction Aging increases the risk of atherosclerotic vascular disease and its complications. Macrophages are pivotal in the pathogenesis of vascular aging, driving inflammation and atherosclerosis progression. NOX4 (NADPH oxidase 4) expression increases with age, correlating with mitochondrial dysfunction, inflammation, and atherosclerosis. We hypothesized that the NOX4-dependent mitochondrial oxidative stress promotes aging-associated atherosclerosis progression by causing metabolic dysfunction and inflammatory phenotype switch in macrophages. Methods We studied atherosclerotic lesion morphology and macrophage phenotype in young (5-month-old) and aged (16-month-old) Nox4 -/-/Apoe -/- and Apoe -/- mice fed Western diet. Results Young Nox4-/-/Apoe-/- and Apoe-/- mice had comparable aortic and brachiocephalic artery atherosclerotic lesion cross-sectional areas. Aged mice showed significantly increased lesion area compared with young mice. Aged Nox4-/-/Apoe-/- had significantly lower lesion areas than Apoe-/- mice. Compared with Apoe-/- mice, atherosclerotic lesions in aged Nox4-/-/Apoe-/- showed reduced cellular and mitochondrial ROS and oxidative DNA damage, lower necrotic core area, higher collagen content, and decreased inflammatory cytokine expression. Immunofluorescence and flow cytometry analysis revealed that aged Apoe-/- mice had a higher percentage of classically activated pro-inflammatory macrophages (CD38+CD80+) in the lesions. Aged Nox4-/-/Apoe-/- mice had a significantly higher proportion of alternatively activated pro-resolving macrophages (EGR2+/CD163+CD206+) in the lesions, with an increased CD38+/EGR2+ cell ratio compared with Apoe-/- mice. Mitochondrial respiration assessment revealed impaired oxidative phosphorylation and increased glycolytic ATP production in macrophages from aged Apoe-/- mice. In contrast, macrophages from Nox4-/-/Apoe-/- mice were less glycolytic and more aerobic, with preserved basal and maximal respiration and mitochondrial ATP production. Macrophages from Nox4-/-/Apoe-/- mice also had lower mitochondrial ROS levels and reduced IL1β secretion; flow cytometry analysis showed fewer CD38+ cells after IFNγ+LPS treatment and more EGR2+ cells after IL4 treatment than in Apoe-/- macrophages. In aged Apoe-/- mice, inhibition of NOX4 activity using GKT137831 significantly reduced macrophage mitochondrial ROS and improved mitochondrial function, resulting in decreased CD68+CD80+ and increased CD163+CD206+ lesion macrophage proportion and attenuated atherosclerosis. Discussion Our findings suggest that increased NOX4 in aging drives macrophage mitochondrial dysfunction, glycolytic metabolic switch, and pro-inflammatory phenotype, advancing atherosclerosis. Inhibiting NOX4 or mitochondrial dysfunction could alleviate vascular inflammation and atherosclerosis, preserving plaque integrity. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Drug-eluting stents versus bare-metal stents in saphenous vein grafts: a double-blind, randomised trial

Author

Brilakis, Emmanouil S, Edson, Robert, Bhatt, Deepak L, Goldman, Steven, Holmes, David R, Rao, Sunil V, Shunk, Kendrick, Rangan, Bavana V, Mavromatis, Kreton, Ramanathan, Kodangudi, Bavry, Anthony A, Garcia, Santiago, Latif, Faisal, Armstrong, Ehrin, Jneid, Hani, Conner, Todd A, Wagner, Todd, Karacsonyi, Judit, Uyeda, Lauren, Ventura, Beverly, Alsleben, Aaron, Lu, Ying, Shih, Mei-Chiung, Banerjee, Subhash, Investigators, DIVA Trial, Ahmed, Bina, Ratliff, D Michelle, Ricciardi, Mark, Sheldon, Mark, Icenogle, Milton, Snider, Richard, Ardati, Amer, Nallamothu, Brahmajee, Duvernoy, Claire, Menees, Daniel S, Gurm, Hitinder, Thomas, Michael P, Grossman, Paul, Owen, Kristine, Topaz, On, Kumar, Gautam, Block, Peter, Zidar, David A, Bezerra, Hiram, Goldberg, Jonathan, Ortiz, Jose, Jozic, Joseph, Osman, Mohammed, Rosenthal, Noah, Parikh, Sahil A, Lassar, Tom A, Chan, Albert, Kumar, Arun, Aggarwal, Kul, Cyrus, Tillmann, Grodin, Jerrold, Hattler, Brack, Casserly, Ivan, Messenger, John, Kim, Michael, Rogers, R Kevin, Waldo, Stephen, Tsai, Thomas, Morris, Kenneth, Krucoff, Mitchell, Rao, Sunil, Povsic, Thomas J, Jones, William S, Bavry, Anthony, Choi, Calvin, Park, Ki, Liu, Jayson, Kar, Biswajit, Paniagua, David, Breall, Jeffrey, Bolad, Islam, Mukerji, Rita, Subbarao, Roopa, Abdel-Latif, Ahmed, Booth, David C, Ziada, Khaled M, Rajan, Lawrence, Hakeem, Abdul, Uretsky, Barry F, Agrawal, Mayank, Sachdeva, Rajesh, Ahmed, Zubair, McGee, Jesse, Shah, Rahman, Sharma, Alok, McFalls, Edward, Siddiqui, Rizwan, and Adabag, Selcuk

Subjects
Cardiovascular, Bioengineering, Clinical Research, Heart Disease, Clinical Trials and Supportive Activities, Patient Safety, Assistive Technology, Atherosclerosis, Heart Disease - Coronary Heart Disease, Aged, Double-Blind Method, Drug-Eluting Stents, Female, Graft Rejection, Humans, Male, Middle Aged, Percutaneous Coronary Intervention, Saphenous Vein, Self Expandable Metallic Stents, Thrombosis, Treatment Outcome, DIVA Trial Investigators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundFew studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions.MethodsPatients were recruited to our double-blind, randomised controlled trial from 25 US Department of Veterans Affairs centres. Eligible participants were aged at least 18 years and had at least one significant de-novo SVG lesion (50-99% stenosis of a 2·25-4·5 mm diameter SVG) requiring percutaneous coronary intervention with intent to use embolic protection devices. Enrolled patients were randomly assigned, in a 1:1 ratio, by phone randomisation system to receive a DES or BMS. Randomisation was stratified by presence or absence of diabetes and number of target SVG lesions requiring percutaneous coronary intervention (one or two or more) within each participating site by use of an adaptive scheme intended to balance the two stent type groups on marginal totals for the stratification factors. Patients, referring physicians, study coordinators, and outcome assessors were masked to group allocation. The primary endpoint was the 12-month incidence of target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularisation. The DIVA trial is registered with ClinicalTrials.gov, number NCT01121224.FindingsBetween Jan 1, 2012, and Dec 31, 2015, 599 patients were randomly assigned to the stent groups, and the data for 597 patients were used. The patients' mean age was 68·6 (SD 7·6) years, and 595 (>99%) patients were men. The two stent groups were similar for most baseline characteristics. At 12 months, the incidence of target vessel failure was 17% (51 of 292) in the DES group versus 19% (58 of 305) in the BMS group (adjusted hazard ratio 0·92, 95% CI 0·63-1·34, p=0·70). Between-group differences in the components of the primary endpoint, serious adverse events, or stent thrombosis were not significant. Enrolment was stopped before the revised target sample size of 762 patients was reached.InterpretationIn patients undergoing stenting of de-novo SVG lesions, no significant differences in outcomes between those receiving DES and BMS during 12 months of follow-up were found. The study results have important economic implications in countries with high DES prices such as the USA, because they suggest that the lower-cost BMS can be used in SVG lesions without compromising either safety or efficacy.FundingUS Department of Veterans Affairs Cooperative Studies Program.

Published
2018

6. Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial

Author

Reynolds, Harmony R., primary, Cyr, Derek D., additional, Merz, C. Noel Bairey, additional, Shaw, Leslee J., additional, Chaitman, Bernard R., additional, Boden, William E., additional, Alexander, Karen P., additional, Rosenberg, Yves D., additional, Bangalore, Sripal, additional, Stone, Gregg W., additional, Held, Claes, additional, Spertus, John, additional, Goetschalckx, Kaatje, additional, Bockeria, Olga, additional, Newman, Jonathan D., additional, Berger, Jeffrey S., additional, Elghamaz, Ahmed, additional, Lopes, Renato D., additional, Min, James K., additional, Berman, Daniel S., additional, Picard, Michael H., additional, Kwong, Raymond Y., additional, Harrington, Robert A., additional, Thomas, Boban, additional, O'Brien, Sean M., additional, Maron, David J., additional, Hochman, Judith S., additional, Mavromatis, Kreton, additional, Linefsky, Jason, additional, Miller, Todd, additional, Banerjee, Subhash, additional, Reynolds, Harmony R., additional, Donnino, Robert M., additional, Phillips, Lawrence M., additional, Saric, Muhamed, additional, Abdul‐Nour, Khaled, additional, Stone, Peter H., additional, Jang, James J., additional, Yee, Gennie, additional, Weitz, Steven, additional, Arnold, Suzanne, additional, O’Keefe, James Henry, additional, Shapiro, Michael D., additional, El‐Hajjar, Mohammad, additional, Sidhu, Mandeep S., additional, Fein, Steven A., additional, Torosoff, Mikhail T., additional, Lyubarova, Radmila, additional, Mookherjee, Sulagna, additional, Drzymalski, Krzysztof, additional, McFalls, Edward O., additional, Garcia, Santiago A., additional, Bertog, Stefan C., additional, Siddiqui, Rizwan A., additional, Ishani, Areef, additional, Hansen, Ronnell A., additional, Khouri, Michel Georges, additional, Goldberg, Jonathan L., additional, Goldweit, Richard, additional, Cohen, Ronny A., additional, Mirrer, Brooks, additional, Navarro, Victor, additional, Winchester, David E., additional, Kronenberg, Marvin, additional, Rogal, Philip, additional, McFarren, Christopher, additional, Heitner, John F., additional, Dauber, Ira M., additional, Cannan, Charles, additional, Sudarshan, Sriram, additional, Mehta, Puja K., additional, McDaniel, Michael, additional, Lerakis, Stamatios, additional, Quyyumi, Arshed, additional, Wenger, Nanette K., additional, Hedgepeth, Chester M., additional, Hurlburt, Heather, additional, Rosen, Alan, additional, Sahul, Zakir, additional, Booth, David, additional, Leung, Steve, additional, Abdel‐Latif, Ahmed, additional, Reda, Hassan, additional, Ziada, Khaled, additional, Setty, Sampoornima, additional, Barua, Rajat S., additional, Hage, Fadi, additional, Caldeira, Christiano, additional, Davies, James E., additional, Leesar, Massoud, additional, Heo, Jaekyeong, additional, Iskandrian, Amy, additional, Al Solaiman, Firas, additional, Singh, Satinder, additional, Dajani, Khaled, additional, Der Mesropian, Paul, additional, Sacco, Joseph, additional, McCandless, Brian, additional, Orgera, Marisa, additional, Arif, Imran, additional, Kerr, Hanan, additional, Trejo (Gutierrez), Jorge F., additional, Fletcher, Gerald, additional, Lane, Gary E., additional, Neeson, Lynn M., additional, Parikh, Pragnesh P., additional, Pollak, Peter M., additional, Shapiro, Brian P., additional, Landolfo, Kevin, additional, Gemignani, Anthony, additional, O’Rourke, Daniel, additional, Meadows, Judith L., additional, Call, Jason T., additional, Hannan, Joseph, additional, Bojar, Robert, additional, Kumar, Deepti, additional, Mukai, John, additional, Martin, Edward T., additional, Vorobiof, Gabriel, additional, Moorman, Alec, additional, Kinlay, Scott, additional, Hamburger, Robert J., additional, Rocco, Thomas P., additional, Bhatt, Deepak L., additional, Croce, Kevin, additional, Quin, Jacquelyn A., additional, Anumpa, Jati, additional, Zenati, Marco, additional, Faxon, David P., additional, Rayos, Glenn, additional, Seedhom, Ashraf, additional, Sullenberger, Lance, additional, Kumkumian, Gregory, additional, Sedlis, Steven P., additional, Donnino, Robert M., additional, Lorin, Jeffrey, additional, Tamis‐Holland, Jacqueline E., additional, Kornberg, Robert, additional, Leber, Robert, additional, Saba, Souheil, additional, Lee, Michael W., additional, Small, Delano R., additional, Nona, Wassim, additional, Alexander, Patrick B., additional, Rehman, Iram, additional, Badami, Umesh, additional, Marzo, Kevin, additional, Robbins, Inga H., additional, Levite, Howard A., additional, Shetty, Sanjay, additional, Patel, Mayuri, additional, Hamroff, Glenn S., additional, Little, Raymond W., additional, Zimbelman, Brandi D., additional, Lui, Charles Y., additional, Smith, Brigham R., additional, Vezina, Daniel P., additional, Khor, Lillian L., additional, Abraham, Josephine D., additional, Bull, David A., additional, McKellar, Stephen H., additional, Kotter, John, additional, Hu, Bob, additional, Labovitz, Arthur J., additional, Berlowitz, Michael, additional, Matar, Fadi, additional, Rodriguez, Fatima, additional, Schnittger, Ingela, additional, Fearon, William F., additional, Deedwania, Prakash, additional, Reddy, Kiran, additional, Sweeny, Joseph, additional, Spizzieri, Christopher, additional, Hochberg, Claudia P., additional, Salerno, William D., additional, Wyman, Ray, additional, Zarka, Amer, additional, Shah, Anil V., additional, Haldis, Thomas, additional, Kohn, Jeffrey A., additional, Girotra, Saket, additional, Almousalli, Omar, additional, Krishnam, Mayil S., additional, Milliken, Jeffrey C., additional, Patel, Pranav M., additional, Seto, Arnold H., additional, Harley, Kevin T., additional, Gibson, Michael A., additional, Allen, Byron J., additional, Coram, Rita, additional, Thomas, Sabu, additional, Schwartz, Ronald G., additional, Chen, Wei, additional, El Shahawy, Mahfouz, additional, Stafford, James, additional, Abernethy, William B., additional, Zurick, Andrew, additional, Meyer, Thomas M., additional, Morford, Ronald G., additional, Rutkin, Bruce, additional, Bokhari, Sabahat, additional, Sokol, Seth I., additional, Meisner, Jay, additional, Hamzeh, Ihab, additional, Misra, Arunima, additional, Wall, Matthew, additional, De Rosen, Veronica Lenges, additional, Alam, Mahboob, additional, Turner, Michael C., additional, Mulhearn, Thomas J., additional, Good, Arnold P., additional, Shammas, Nicolas W., additional, Chilton, Robert, additional, Nguyen, Patricia K., additional, Jezior, Matthew, additional, Gordon, Paul C., additional, Crain, Thomas, additional, Stenberg, Robert, additional, Pedalino, Ronald P., additional, Wiesel, Joseph, additional, Juang, George J., additional, Al‐Amoodi, Mohammed, additional, Wohns, David, additional, Lader, Ellis W., additional, Mumma, Michael, additional, Dharmarajan, Lekshmi, additional, McGarvey, Joseph F. X., additional, Downes, Thomas R., additional, Luckasen, Gary J., additional, Cheong, Benjamin, additional, Potluri, Srinivasa, additional, Mastouri, Ronald A., additional, Breall, Jeffery A., additional, Revtyak, George E., additional, Bazeley, Jonathan W., additional, Li, Dayuan, additional, Giedd, Kenneth, additional, Old, Wayne, additional, Burt, Francis, additional, Sokhon, Kozhaya, additional, Gopal, Deepika, additional, Valeti, Uma S., additional, Kobashigawa, Jon, additional, Govindan, Sajeev Chakanalil, additional, Nair, Rajesh Gopalan, additional, Manjunath, Cholenahally Nanjappa, additional, Moorthy, Nagaraja, additional, Manjunath, Satvic Cholenahally, additional, Narayanappa, Suryaprakash, additional, Pandit, Neeraj, additional, Nath, Ranjit Kumar, additional, Dwivedi, S. K., additional, Narain, V. S., additional, Chandra, Sharad, additional, Wander, Gurpreet S., additional, Tandon, Rohit, additional, Ralhan, Sarju, additional, Aslam, Naved, additional, Goyal, Abhishek, additional, Bhargava, Balram, additional, Karthikeyan, G., additional, Ramakrishnan, S., additional, Seth, Sandeep, additional, Yadav, Rakesh, additional, Singh, Sandeep, additional, Roy, Ambuj, additional, Parakh, Neeraj, additional, Verma, Sunil Kumar, additional, Narang, Rajiv, additional, Mishra, Sundeep, additional, Naik, Nitish, additional, Sharma, Gautam, additional, Choudhary, Shiv Kumar, additional, Patel, Chetan, additional, Gulati, Gurpreet, additional, Sharma, Sanjeev, additional, Bahl, V. K., additional, Mathew, Anoop, additional, Punnoose, Eapen, additional, Gadkari, Milind Avdhoot, additional, Gadage, Siddharth, additional, Pillay, Tapan Umesh, additional, Satheesh, Santhosh, additional, Mathur, Atul, additional, Kaul, Upendra, additional, Christopher, Johann, additional, Menon, Rajeev, additional, Kumar, Nirmal, additional, Oomman, Abraham, additional, Mao, Robert, additional, Solomon, Hilda, additional, Naik, Sudhir, additional, Khan, Sajeeda Parveen, additional, Grant, Purvez, additional, Kachru, Ranjan, additional, Ajit Kumar, V. K., additional, Ganapathi, Sanjay, additional, Jayakumar, K., additional, Sivadasanpillai, Harikrishnan, additional, Sasidharan, Bijulal, additional, Kapilamoorthy, T. R., additional, Polamuri, Praneeth, additional, Senior, Roxy, additional, Gurunathan, Sothinathan, additional, Karogiannis, Nikolaos, additional, Shah, Benoy N., additional, Trimlett, Richard HJ, additional, Rubens, Michael B., additional, Nicol, Edward D., additional, Mittal, Tarun K., additional, Hampson, Reinette, additional, Gamma, Reto Andreas, additional, de Belder, Mark A., additional, Thambyrajah, Jeet, additional, Nageh, Thuraia, additional, Davies, John R., additional, Lindsay, Steven J., additional, Kurian, John, additional, Jamil, Haqeel, additional, Raheem, Osama, additional, Hoye, Angela, additional, Donnelly, Patrick, additional, Valecka, Bernardas, additional, Chauhan, Anoop, additional, Barr, Craig, additional, Alfakih, Khaled, additional, Byrne, Jonathan, additional, Webb, Ian, additional, Henriksen, Peter, additional, OKane, Peter, additional, de Silva, Ramesh, additional, Conway, Dwayne S. G., additional, Sirker, Alexander A, additional, Hoole, Stephen P., additional, Witherow, Fraser N., additional, Johnston, Nicola, additional, Harbinson, Mark, additional, Walsh, Simon, additional, Douglas, Hanna, additional, Luckie, Matthew, additional, Sobolewska, Jolanta, additional, Jeetley, Paramjit, additional, Patel, Niket, additional, Kotecha, Tushar, additional, Travill, Christopher, additional, Karimullah, Iqbal, additional, Al‐Bustami, Mahmud, additional, Braganza, Denise, additional, Henderson, Robert, additional, Pointon, Kate, additional, Naik, Surendra, additional, Mathew, Thomas, additional, Berry, Colin, additional, Collison, Damien, additional, Roditi, Giles, additional, Moriarty, Andrew J., additional, Glover, Jason D., additional, Pradhan, Jiwan, additional, Mikhail, Ghada, additional, Francis, Darrel P., additional, Gosselin, Gilbert, additional, Diaz, Ariel, additional, Rheault, Philippe, additional, Barrero, Miguel, additional, Gagné, Carl‐Éric, additional, Pépin‐Dubois, Yanek, additional, Costa, Ricardo, additional, Sia, Ying Tung, additional, Lemay, Catherine, additional, Gisbert, Alejandro, additional, Gervais, Pierre, additional, Rheault, Alain, additional, Phaneuf, Denis Carl, additional, Garg, Pallav, additional, Chow, Benjamin J. W., additional, Hessian, Renee C., additional, Beanlands, Rob S., additional, Davies, Richard F., additional, Bainey, Kevin R., additional, Cheema, Asim N., additional, Bagai, Akshay, additional, Wald, Ron, additional, Goodman, Shaun, additional, Graham, John Joseph, additional, Peterson, Mark, additional, Chow, Chi‐Ming, additional, Abramson, Beth, additional, Cheema, Asim Nazir, additional, Vakani, Mohammad Tariq, additional, Cha, James, additional, Howarth, Andrew G, additional, Wong, Graham, additional, Uxa, Amar, additional, Galiwango, Paul, additional, Kassam, Saleem, additional, Mukherjee, Ashok, additional, Ricci, A. Joseph, additional, Lam, Andy, additional, Mehta, Shamir, additional, Udell, Jacob, additional, Généreux, Philippe, additional, Hameed, Adnan, additional, Daba, Ledjalem, additional, Hueb, Whady, additional, Rezende, Paulo Cury, additional, Silva, Expedito Eustáquio Ribeiro, additional, Hueb, Alexandre Ciappina, additional, Smanio, Paola Emanuela Poggio, additional, de Quadros, Alexandre Schaan, additional, Kalil, Renato Abdala Karam, additional, da Costa Vieira, José Luiz, additional, Grossmann, Gabriel, additional, de Oliveira, Pedro Píccaro, additional, Bridi, Leonardo, additional, Savaris, Simone, additional, Vitola, João V., additional, Cerci, Rodrigo J., additional, Farias, Fabio R., additional, Fernandes, Miguel M., additional, Marin‐Neto, José Antonio, additional, Schmidt, André, additional, de Oliveira Lima Filho, Moysés, additional, Oliveira, Ricardo Mendes, additional, Chierice, João Reynaldo Abbud, additional, Polanczyk, Carísi A., additional, Furtado, Mariana V., additional, Smidt, Luis F., additional, Carvalho, Antonio Carlos, additional, Pucci, Gustavo, additional, Lyra, Flavio, additional, Junior, Alvaro Rabelo Alves, additional, Dracoulakis, Marianna D. A., additional, Lima, Rodolfo G. S. D, additional, Figueiredo, Estevao, additional, Caramori, Paulo Ricardo, additional, Tumelero, Rogerio, additional, Dall’Orto, Frederico, additional, Mesquita, Claudio T., additional, Colafranseschi, Alexandre S., additional, Oliveira, Amarino C., additional, Carvalho, Luiz A., additional, Palazzo, Isabella C., additional, Sousa, Andre S., additional, da Silva, Expedito Eustáquio Ribeiro, additional, de Barros, Pedro Gabriel Melo, additional, de Pádua Silva Baptista, Luciana, additional, Rodrigues, Marcelo Jamus, additional, de Resende, Marcos Valério Coimbra, additional, Saraiva, Jose Francisco, additional, Costantini, Costantino, additional, Demkow, Marcin, additional, Pracon, Radoslaw, additional, Kepka, Cezary, additional, Teresinska, Anna, additional, Kryczka, Karolina, additional, Henzel, Jan, additional, Solecki, Mateusz, additional, Kaczmarska, Edyta, additional, Mazurek, Tomasz, additional, Drozdz, Jaroslaw, additional, Czarniak, Bartosz, additional, Frach, Malgorzata, additional, Szymczyk, Konrad, additional, Niedzwiecka, Iwona, additional, Sobczak, Sebastian, additional, Ciurus, Tomasz, additional, Jakubowski, Piotr, additional, Misztal‐Teodorczyk, Magdalena, additional, Teodorczyk, Dawid, additional, Fratczak, Aleksandra, additional, Szkopiak, Marcin, additional, Lebioda, Patrycja, additional, Wlodarczyk, Michal, additional, Plachcinska, Anna, additional, Kusmierek, Jacek, additional, Miller, Magdalena, additional, Marciniak, Halina, additional, Wojtczak‐Soska, Karolina, additional, Luczak, Katarzyna, additional, Tarchalski, Tomasz, additional, Cichocka‐Radwan, Anna, additional, Szwed, Hanna, additional, Szulczyk, Grazyna Anna, additional, Witkowski, Adam, additional, Kukula, Krzysztof, additional, Celinska‐Spodar, Malgorzta, additional, Zalewska, Joanna, additional, Gajos, Grzegorz, additional, Bury, Krzysztof, additional, Pruszczyk, Piotr, additional, Roik, Marek, additional, Loboz‐Grudzien, Krystyna, additional, Sokalski, Leszek, additional, Brzezinska, Barbara, additional, Lesiak, Maciej, additional, Lanocha, Magdalena, additional, Reczuch, Krzysztof W., additional, Kalarus, Zbigniew, additional, Swiatkowski, Andrzej, additional, Szulik, Mariola, additional, Musial, Wlodzimierz J., additional, Bockeria, Leo, additional, Petrosyan, Karen, additional, Trifonova, Tatiana, additional, Chernyavskiy, Alexander M., additional, Kretov, Evgeniy I., additional, Grazhdankin, Igor O., additional, Bershtein, Leonid L., additional, Sayganov, Sergey A., additional, Kuzmina‐Krutetskaya, Anastasia M., additional, Zbyshevskaya, Elizaveta V., additional, Katamadze, Nana O., additional, Demchenko, Elena A., additional, Kozlov, Pavel S., additional, Kozulin, Vikentiy Y., additional, Lubinskaya, Ekaterina I., additional, Lopez‐Sendon, Jose, additional, Castro, Almudena, additional, Salicio, Elena Refoyo, additional, Guzman, Gabriela, additional, Galeote, Gabriel, additional, Valbuena, Silvia, additional, Peteiro, Jesús, additional, Martínez‐Ruíz, María Dolores, additional, Pérez‐Fernández, Ruth, additional, Cuenca‐Castillo, José J., additional, Flores‐Ríos, Xacobe, additional, Prada‐Delgado, Óscar, additional, Barge‐Caballero, Gonzalo, additional, Juanatey, Jose Ramon Gonzalez, additional, Bayarri, Miguel Souto, additional, Nuñez, Virginia Pubull, additional, Sanchez, Raymundo Ocaranza, additional, Alvarez, Belen Cid, additional, Gil, Carlos Peña, additional, Monzonis, Amparo Martinez, additional, Sionis, Alessandro, additional, Perales, Montserrat Vila, additional, Padró, Josep Maria, additional, Peñaranda, Antonio Serra, additional, Picart, Joan García, additional, Iglesias, Antonino Ginel, additional, Marimon, Xavier Garcia‐Moll, additional, Lladó, Guillem Pons, additional, Costa, Francesc Carreras, additional, Miro, Vicente, additional, Diez, Jose L., additional, Calvillo, Pilar, additional, Ortuño, F. Marin, additional, Chávarri, M. Valdés, additional, Montolliu, A. Tello, additional, Bermudez, E. Pinar, additional, De La Morena, G., additional, Blancas, Montserrat Gracida, additional, Luena, Jose Enrique Castillo, additional, Fernandez‐Aviles, Francisco, additional, Chen, Jiyan, additional, Wu, Yongjian, additional, Ma, Yitong, additional, Yang, Yining, additional, Ji, Zheng, additional, Yang, Xinchun, additional, Lin, Wenhua, additional, Zeng, Hesong, additional, Fu, Xin, additional, Yang, Bin, additional, Wang, Songtao, additional, Cheng, Gong, additional, Zhao, Yulan, additional, Fang, Xuehua, additional, Zeng, Qiutang, additional, Su, Xi, additional, Li, Qingxian, additional, Nie, Shao‐ping, additional, Yu, Qin, additional, Wang, Jian’an, additional, Zhang, Shuyang, additional, Liu, Zhenyu, additional, Perna, Gian Piero, additional, Marini, Marco, additional, Gabrielli, Gabriele, additional, Provasoli, Stefano, additional, Verna, Edoardo, additional, Monti, Lorenzo, additional, Nardi, Barbara, additional, Di Chiara, Antonio, additional, Mortara, Andrea, additional, Galvani, Marcello, additional, Ottani, Filippo, additional, Sicuro, Marco, additional, Calabro, Paolo, additional, Formisano, Tiziana, additional, Tarantini, Giuseppe, additional, Cucchini, Umberto, additional, Andres, Anto Luigi, additional, Racca, Emanuela, additional, Briguori, Carlo, additional, Amati, Roberto, additional, Vergoni, William, additional, Russo, Aldo, additional, Fanelli, Raffaele, additional, Poh, Kian‐Keong, additional, Chai, Ping, additional, Lau, Titus, additional, Loh, Joshua P., additional, Tay, Edgar L., additional, Teoh, Kristine, additional, Teo, Lynette L., additional, Ong, Ching‐Ching, additional, Wong, Raymond C., additional, Loh, Poay‐Huan, additional, Kofidis, Theodoros, additional, Chan, Wan Xian, additional, Chan, Koo Hui, additional, Foo, David, additional, Kong, Jason Loh Kwok, additional, Er, Ching Min, additional, Jafary, Fahim Haider, additional, Chua, Terrance, additional, Doerr, Rolf, additional, Stumpf, Juergen, additional, Matschke, Klaus, additional, Simonis, Gregor, additional, Kadalie, Clemens T., additional, Sechtem, Udo, additional, Ong, Peter, additional, Schulze, P. Christian, additional, Goebel, Bjoern, additional, Lenk, Karsten, additional, Nickenig, Georg, additional, Schuchlenz, Herwig, additional, Weikl, Stefan, additional, Lang, Irene Marthe, additional, Huber, Kurt, additional, Jakl‐Kotauschek, Gabriele, additional, Vertes, Andras, additional, Varga, Albert, additional, Fontos, Geza, additional, Merkely, Bela, additional, Kerecsen, Gabor, additional, Hinic, Sasa, additional, Zdravkovic, Marija, additional, Mudrenovic, Vladan, additional, Crnokrak, Bogdan, additional, Beleslin, Branko D., additional, Boskovic, Nikola N., additional, Petrovic, Marija T., additional, Dobric, Milan R., additional, Markovic, Zeljko Z., additional, Mladenovic, Ana S., additional, Cemerlic‐Adjic, Nada, additional, Davidovic, Goran, additional, Vucic, Rada, additional, Dekleva, Milica Nikola, additional, Stankovic, Goran, additional, Apostolovic, Svetlana, additional, Escobedo, Jorge, additional, Baleón‐Espinosa, Rubén, additional, Campos‐Santaolalla, Arturo S., additional, Durán‐Cortés, Elihú, additional, Flores‐Palacios, José M., additional, García‐Rincón, Andrés, additional, Jiménez‐Santos, Moisés, additional, Peñafiel, Joaquín V., additional, Ortega‐Ramírez, José A., additional, Valdespino‐Estrada, Aquiles, additional, Rosas, Erick Alexánderson, additional, Selvanayagam, Joseph B., additional, Joseph, Majo X., additional, Thambar, Suku T., additional, Beltrame, John F., additional, Hillis, Graham S., additional, Thuaire, Christophe, additional, Dutoiu, Téodora, additional, Steg, Philippe Gabriel, additional, Juliard, Jean‐Michel, additional, Slama, Michel S., additional, El Mahmoud, Rami, additional, Nicollet, Eric, additional, Goube, Pascal, additional, Barone‐Rochette, Gilles, additional, Furber, Alain, additional, Bière, Loïc, additional, Laucevicius, Aleksandras, additional, Celutkiene, Jelena, additional, Kedhi, Elvin, additional, Timmer, Jorik, additional, Hermanides, Rik, additional, Kaplan, Eliza, additional, Riezebos, Robert K., additional, Samadi, Pouneh, additional, van Dongen, Elise, additional, Niehe, Sander R., additional, Suryapranata, Harry, additional, van Vugt, Stijn, additional, Ramos, Ruben, additional, Cacela, Duarte, additional, Santana, Ana, additional, Fiarresga, Antonio, additional, Sousa, Lidia, additional, Marques, Hugo, additional, Patricio, Lino, additional, Bernanrdes, Luis, additional, Rio, Pedro, additional, Carvalho, Ramiro, additional, Ferreira, Rui, additional, Silva, Tiago, additional, Rodrigues, Ines, additional, Modas, Pedro, additional, Portugal, Guilherme, additional, Fragata, Jose, additional, Pinto, Fausto J., additional, Menezes, Miguel Nobre, additional, Lopes, Guilhermina Cantinho, additional, Almeida, Ana Gomes, additional, Silva, Pedro Canas, additional, Nobre, Angelo, additional, Francisco, Ana Rita, additional, Ferreira, Nuno, additional, Lopes, Ricardo L., additional, Guzman, Luis, additional, Figal, Julio César, additional, Méndiz, Oscar, additional, Cortés, Claudia, additional, Favaloro, Roberto René, additional, Alvarez, Carlos, additional, Courtis, Javier, additional, Zeballos, Gabriela, additional, Schiavi, Lilia, additional, Rubio, Mariano, additional, Devlin, Gerard Patrick, additional, Fisher, Raewyn, additional, Stewart, Ralph Alan Huston, additional, White, Harvey Douglas, additional, Benatar, Jocelyne, additional, Kedev, Sasko, additional, Mitevska, Irena Peovska, additional, Kostovska, Elizabeta Srbinovska, additional, Pejkov, Hristo, additional, Eggers, Kai, additional, Frostfelt, Gunnar, additional, Johnston, Nina, additional, Olsowka, Maciej, additional, Åkerblom, Axel, additional, Soveri, Inga, additional, Aspberg, Johannes, additional, Sharir, Tali, additional, Elian, Dan, additional, Kerner, Arthur, additional, Massalha, Samia, additional, Fukuda, Keiichi, additional, Kohsaka, Shun, additional, Yasuda, Satoshi, additional, Nishimura, Shigeyuki, additional, Van de Werf, Frans, additional, Claes, Kathleen, additional, Hung, Chung‐Lieh, additional, Yun, Chun‐Ho, additional, Hou, Charles Jia‐Yin, additional, Kuo, Jen‐Yuan, additional, Yeh, Hung‐I, additional, Hung, Ta‐Chuan, additional, Li, Jiun‐Yi, additional, Chien, Chen‐Yen, additional, Tsai, Cheng‐Ting, additional, Liu, Chun‐Chieh, additional, Yu, Fa‐Chang, additional, Lin, Yueh‐Hung, additional, Lan, Wei‐Ren, additional, Yen, Chih‐Hsuan, additional, Tsai, Jui‐Peng, additional, Sung, Kuo‐Tzu, additional, Ntsekhe, Mpiko, additional, Pandie, Shaheen, additional, Viljoen, Charle A., additional, De Andrade, Marianne, additional, Moccetti, Tiziano, additional, Rossi, M. Grazia, additional, Abdelhamid, Magdy, additional, Adel, Ahmed, additional, Kamal, Ahmed, additional, Mahrous, Hossam, additional, El Kaffas, Sameh, additional, El Fishawy, Hussien, additional, Pop, Calin, additional, Claudia, Matei, additional, Popescu, Bogdan A., additional, Ginghina, Carmen, additional, Deleanu, Dan, additional, Iliescu, Vlad A., additional, Al‐Mallah, Mouaz H., additional, Aljzeeri, Ahmed, additional, Najm, Hani, additional, Alghamdi, Ali, additional, Ramos, Walter Enrique Mogrovejo, additional, Kuanprasert, Srun, additional, Prommintikul, Arintaya, additional, Nawarawong, Weerachai, additional, Woragidpoonpol, Surin, additional, Tepsuwan, Thitipong, additional, Taksaudom, Noppon, additional, Rimsukcharoenchai, Chataroon, additional, Euathrongchit, Juntima, additional, Wannasopha, Yutthaphan, additional, Yamwong, Sukit, additional, Sritara, Piyamitr, additional, Aramcharoen, Suthara, additional, Meemuk, Krissada, additional, Khairuddin, Ahmad, additional, Hadi, Hafidz Abd, additional, and Yahaya, Shaiful Azmi, additional

Published
2024
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15. Attenuation of ER stress prevents post-infarction-induced cardiac rupture and remodeling by modulating both cardiac apoptosis and fibrosis

Author

Luo, Tao, Kim, Jin Kyung, Chen, Baihe, Abdel-Latif, Ahmed, Kitakaze, Masafumi, and Yan, Liang

Subjects
Heart Disease, Cardiovascular, Heart Disease - Coronary Heart Disease, 2.1 Biological and endogenous factors, Aetiology, Animals, Animals, Newborn, Apoptosis, Apoptosis Regulatory Proteins, Blotting, Western, Cell Survival, Endoplasmic Reticulum Stress, Fibrosis, Heart Rupture, Male, Membrane Potential, Mitochondrial, Mice, Mice, Inbred C57BL, Myocardial Infarction, Phenylbutyrates, Random Allocation, Rats, Rats, Sprague-Dawley, ER stress, Myocardial infarction, Cardiac rupture, Cardiac remodeling, Biochemistry and Cell Biology, Toxicology
Abstract

Endoplasmic reticulum (ER) stress is implicated in the pathophysiology of various cardiovascular diseases, but the role of ER stress in cardiac rupture and/or remodeling after myocardial infarction (MI) is still unclear. Here we investigated whether ER stress plays a major role for these processes in mice. We ligated the left coronary artery (LCA) without reperfusion in mice and administered either NaCl or 4-phenylbutyric acid (4-PBA, 20 mg/kg/d) intraperitoneally for 4 weeks. Cardiac rupture rates during the first week of MI were 37.5% and 18.2% in the control and 4-PBA groups, respectively. The extent of ventricular aneurysm and fibrosis was less, and the cardiac function better, in the 4-PBA group compared with the control group. The protein levels of ER stress markers in the heart tissues of the control group remained elevated during the entire 4-week period after MI, while pro-apoptotic proteins mainly increased in the early phase, and the pro-fibrotic proteins markedly increased in the late phase post MI; 4-PBA decreased all of these protein levels. In the primary cultured neonatal rat cardiomyocytes or fibroblasts, hypoxia (3% O2) increased the number of apoptotic cardiomyocytes and promoted the proliferation and migration of fibroblasts, all of which were attenuated by 4-PBA (0.5 mM). These findings indicate that MI induces ER stress and provokes cardiac apoptosis and fibrosis, culminating in cardiac rupture and remodeling, and that the attenuation of ER stress could be an effective therapeutic target to prevent post-MI complications.

Published
2015

26. Neutrophil-Derived S100A8/A9 Amplify Granulopoiesis After Myocardial Infarction

Author

Sreejit, Gopalkrishna, Abdel-Latif, Ahmed, Athmanathan, Baskaran, Annabathula, Rahul, Dhyani, Ashish, Noothi, Sunil K., Quaife-Ryan, Gregory A., Al-Sharea, Annas, Pernes, Gerard, Dragoljevic, Dragana, Lal, Hind, Schroder, Kate, Hanaoka, Beatriz Y., Raman, Chander, Grant, Maria B., Hudson, James E., Smyth, Susan S., Porrello, Enzo R., Murphy, Andrew J., and Nagareddy, Prabhakara R.

Published
2020
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33. Prognostic Significance of Activated Monocytes in Patients with ST-Elevation Myocardial Infarction.

Author

Abo-Aly, Mohamed, Shokri, Elica, Chelvarajan, Lakshman, Tarhuni, Wadea M., Tripathi, Himi, and Abdel-Latif, Ahmed

Subjects
ST elevation myocardial infarction, MONOCYTES, CORONARY artery disease, PROPORTIONAL hazards models, MYOCARDIAL infarction, PERCUTANEOUS coronary intervention
Abstract

Circulating monocytes have different subsets, including classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++), which play different roles in cardiovascular physiology and disease progression. The predictive value of each subset for adverse clinical outcomes in patients with coronary artery disease is not fully understood. We sought to evaluate the prognostic efficacy of each monocyte subset in patients with ST-elevation myocardial infarction (STEMI). We recruited 100 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). Blood samples were collected at the time of presentation to the hospital (within 6 h from onset of symptoms, baseline (BL)) and then at 3, 6, 12, and 24 h after presentation. Monocytes were defined as CD45+/HLA-DR+ and then subdivided based on the expression of CD14, CD16, CCR2, CD11b, and CD42. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, stent thrombosis, in-stent restenosis, and recurrent myocardial infarction. Univariate and multivariate Cox proportional hazards models, including baseline comorbidities, were performed. The mean age of our cohort was 58.9 years and 25% of our patients were females. Patients with high levels (above the median) of CD14+CD16++ monocytes showed an increased risk for the primary endpoint in comparison to patients with low levels; adjusted hazard ratio (aHR) for CD14+/CD16++ cells was 4.3 (95% confidence interval (95% CI) 1.2–14.8, p = 0.02), for CD14+/CD16++/CCR2+ cells was 3.82 (95% CI 1.06–13.7, p = 0.04), for CD14+/CD16++/CD42b+ cells was 3.37 (95% CI 1.07–10.6, p = 0.03), for CD14+/CD16++/CD11b+ was 5.17 (95% CI 1.4–18.0, p = 0.009), and for CD14+ HLA-DR+ was 7.5 (95% CI 2.0–28.5, p = 0.002). CD14++CD16−, CD14++CD16+, and their CD11b+, CCR2+, and CD42b+ aggregates were not significantly predictive for our composite endpoint. Our study shows that CD14+ CD16++ monocytes and their subsets expressing CCR2, CD42, and CD11b could be important predictors of clinical outcomes in patients with STEMI. Further studies with a larger sample size and different coronary artery disease phenotypes are needed to verify the findings. [ABSTRACT FROM AUTHOR]

Published
2023
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36. Adipose Tissue Macrophages Promote Myelopoiesis and Monocytosis in Obesity

Author

Nagareddy, Prabhakara R., Kraakman, Michael, Masters, Seth L., Stirzaker, Roslynn A., Gorman, Darren J., Grant, Ryan W., Dragoljevic, Dragana, Hong, Eun Shil, Abdel-Latif, Ahmed, Smyth, Susan S., Choi, Sung Hee, Korner, Judith, Bornfeldt, Karin E., Fisher, Edward A., Dixit, Vishwa Deep, Tall, Alan R., Goldberg, Ira J., and Murphy, Andrew J.

Published
2014
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41. PreSERVE-AMI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients With Left Ventricular Dysfunction Post STEMI

Author

Quyyumi, Arshed A., Vasquez, Alejandro, Kereiakes, Dean J., Klapholz, Marc, Schaer, Gary L., Abdel-Latif, Ahmed, Frohwein, Stephen, Henry, Timothy D., Schatz, Richard A., Dib, Nabil, Toma, Catalin, Davidson, Charles J., Barsness, Gregory W., Shavelle, David M., Cohen, Martin, Poole, Joseph, Moss, Thomas, Hyde, Pamela, Kanakaraj, Anna Maria, Druker, Vitaly, Chung, Amy, Junge, Candice, Preti, Robert A., Smith, Robin L., Mazzo, David J., Pecora, Andrew, and Losordo, Douglas W.

Published
2017
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44. Sex Differences in Trends and In‐Hospital Outcomes Among Patients With Critical Limb Ischemia: A Nationwide Analysis

Author

Elbadawi, Ayman, Barssoum, Kirolos, Megaly, Michael, Rai, Devesh, Elsherbeeny, Ahmed, Mansoor, Hend, Shishehbor, Mehdi H., Abdel‐Latif, Ahmed, Gulati, Martha, and Elgendy, Islam Y.

Subjects
Chronic Limb-Threatening Ischemia, Male, critical limb ischemia, Databases, Factual, mortality, Interventional Cardiology, body regions, Treatment Outcome, Peripheral Vascular Disease, RC666-701, Vascular Disease, Humans, sex, Diseases of the circulatory (Cardiovascular) system, Female, revascularization, Hospital Mortality, women, Sex Distribution, Original Research
Abstract

Background Critical limb ischemia (CLI) represents the most severe form of peripheral artery disease and is associated with significant mortality and morbidity. Contemporary data comparing the sex differences in trends, revascularization strategies, and in‐hospital outcomes among patients with CLI are scarce. Methods and Results Using the National Inpatient Sample database years 2002 to 2015, we identified hospitalizations for CLI. Temporal trends for hospitalizations for CLI were evaluated. The differences in demographics, revascularization, and in‐hospital outcomes between both sexes were compared. Among 2 400 778 CLI hospitalizations, 43.6% were women. Women were older and had a higher prevalence of obesity, hypertension, heart failure, and prior stroke. Women were also less likely to receive any revascularization (34.7% versus 35.4%, P

Published
2021

46. The Effect of Purification Units for Drinking Water Spread in Al-Alam and Al-Bu Ajil on Heavy Metals

Author

Amjad Abdel-Latif Ahmed Alluhaiby, Saadat Mustafa, and Shaima Fateh

Abstract

The current study was carried out on the treatment and treatment units located in the district of Al-Alam and the village of Al-Bu Ajil, which are located near the Tigris River, with two stations for each region for the period from September 2020 to February 2021, as two samples were collected for each treatment unit by a sample before treatment and a sample after treatment. Iron values ??ranged between (0-0.9) mg / liter before and after treatment, and they ranged between (0-0.05) mg / liter, and zinc values ??were recorded values ??ranging between (0-0.9) mg / liter. Before treatment and after treatment, it ranged between (0-0.05) mg / liter, while the aluminum values ??were relatively few, as values ??ranged between (0.03_0) mg / liter. As for the values ??after treatment, they were (0) mg / liter. Cadmium values ??were between (0,1_0) mg / liter. In the samples after treatment also, all values ??were (0) mg / liter in all stations, and the nickel values ??ranged between (0,9_0) mg / liter in the samples before treatment and after treatment. The values ??were all (0) mg / liter in both stations, and the copper values ??were very low in the mentioned areas, as values ??ranged between (0.1_0) mg / liter before treatment and after treatment, the values ??were (0) mg / liter. In both stations, the purification plants proved their high efficiency in filtering water from heavy elements, and the samples after treatment were in conformity with the Iraqi standards for drinking water. It is worth noting that the purification plants in the areas of Al-Alam and Al-Bu Ajil need a constant monthly maintenance and a replacement process for the filters as they draw their water from wells.

Published
2021

49. Comparative Effectiveness of Anti-Inflammatory Drug Treatments in Coronary Heart Disease Patients: A Systematic Review and Network Meta-Analysis

Author

Wudexi, Ivan, Shokri, Elica, Abo-Aly, Mohamed, Shindo, Kazuhiro, and Abdel-Latif, Ahmed

Subjects
Article Subject
Abstract

Introduction and Hypothesis. The role of inflammation is widely recognized in the pathogenesis of coronary artery disease. Research on animal models had shown the potential benefits of targeting specific inflammatory pathways. However, studies on human subjects are limited with small number of patients and no head-to-head comparisons. Methods. We conducted a network meta-analysis of randomized controlled trials that studied the effects of anti-inflammatory medications on cardiovascular outcomes of coronary artery disease patients. We searched the electronic database until March 2020 for relevant studies. Results. Nineteen trials examining the efficacy of eight anti-inflammatory medications (pexelizumab, anakinra, colchicine, darapladib, varespladib, canakinumab, inclacumab, and losmapimod) were selected for analysis. Overall, there is no statistically significant difference in all-cause mortality, cardiovascular mortality, revascularization, and major cardio and cerebrovascular events (MACCE) with the use of anti-inflammatory drugs. However, we found the use of colchicine significantly reduces the odds of developing stroke by approximately 75% (OR 0.26, CI 0.10-0.63). Colchicine use was also associated with a lower risk of revascularization and MACCE compared to the other agents. Our subgroup analyses comparing the timing of medication initiation (within 7 days vs. >7 days) and clinical presentation (ACS vs. non-ACS) revealed a significant reduction in the risk of recurrent MI in the group that received medication after seven days (OR 0.92, CI 0.86-0.99) and the non-ACS group (OR 0.88, CI 0.80-0.98). Conclusion. Although many anti-inflammatory medications have failed to reduce adverse cardiovascular outcomes in the CAD population, selected medications show promise among subgroups of patients without ACS or after the first week following an acute ischemic event. Future studies examining the proper timing and targetable anti-inflammatory pathways are warranted.

Published
2021
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