Mechanisms of Disease: apoptosis in heart failure-seeing hope in death
The loss of cardiomyocytes in failing or cardiomyopathic hearts is gradual and not accompanied by inflammation or major histomorphologic deformity. Apoptosis, therefore, seems to be the most logical mechanism of cell death. In this Review, Narula et al . discuss the role of apoptosis in systolic dys...
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creator | Narula, Jagat Haider, Nezam Arbustini, Eloisa Chandrashekhar, Y |
description | The loss of cardiomyocytes in failing or cardiomyopathic hearts is gradual and not accompanied by inflammation or major histomorphologic deformity. Apoptosis, therefore, seems to be the most logical mechanism of cell death. In this Review, Narula
et al
. discuss the role of apoptosis in systolic dysfunction and heart failure, and in the development of novel strategies for the management of heart failure.
Apoptosis or programmed cell death is an evolutionarily conserved process of cell death, wherein cells die without provoking significant inflammatory response. There is convincing evidence that apoptosis contributes to the progression of heart failure. Apoptosis occurs through a cascade of subcellular events including cytochrome
c
release into the cytoplasm and activation of proteolytic caspases. Activated caspases lead to fragmentation of cytoplasmic proteins, including contractile apparatus, to a variable extent. It is proposed that the release of cytochrome
c
from mitochondria and contractile protein loss in living heart muscle cells contributes to systolic dysfunction. Interestingly, despite extensive changes in the cytoplasm, nuclear damage, which is the final event in apoptosis, is rather infrequent in the failing heart. Since the nucleus remains unaffected and the genetic blueprint intact in cells with interrupted apoptosis, these heart muscle cells might be amenable to cytoplasmic reconstitution. This process of '
apoptosis interruptus
' could allow development of novel strategies to reverse or attenuate heart failure.
Key Points
Heart failure is a major cardiovascular health problem worldwide
Heart failure is characterized by inexorable progression of systolic dysfunction through the process of adverse cardiac remodeling even after the initial, causal injury has abated
Understanding the pathophysiological substrates of cardiac remodeling can help in the development of novel strategies for prevention, arrest and reversal of the remodeling process
Apoptosis plays a pivotal role in heart failure. Although the apoptotic cascade is initiated, it does not complete in heart failure ('
apoptosis interruptus
')
Interrupted apoptosis reconfirms that heart failure could often be a reversible disease state, and offers an attractive target for management |
doi_str_mv | 10.1038/ncpcardio0710 |
format | Article |
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et al
. discuss the role of apoptosis in systolic dysfunction and heart failure, and in the development of novel strategies for the management of heart failure.
Apoptosis or programmed cell death is an evolutionarily conserved process of cell death, wherein cells die without provoking significant inflammatory response. There is convincing evidence that apoptosis contributes to the progression of heart failure. Apoptosis occurs through a cascade of subcellular events including cytochrome
c
release into the cytoplasm and activation of proteolytic caspases. Activated caspases lead to fragmentation of cytoplasmic proteins, including contractile apparatus, to a variable extent. It is proposed that the release of cytochrome
c
from mitochondria and contractile protein loss in living heart muscle cells contributes to systolic dysfunction. Interestingly, despite extensive changes in the cytoplasm, nuclear damage, which is the final event in apoptosis, is rather infrequent in the failing heart. Since the nucleus remains unaffected and the genetic blueprint intact in cells with interrupted apoptosis, these heart muscle cells might be amenable to cytoplasmic reconstitution. This process of '
apoptosis interruptus
' could allow development of novel strategies to reverse or attenuate heart failure.
Key Points
Heart failure is a major cardiovascular health problem worldwide
Heart failure is characterized by inexorable progression of systolic dysfunction through the process of adverse cardiac remodeling even after the initial, causal injury has abated
Understanding the pathophysiological substrates of cardiac remodeling can help in the development of novel strategies for prevention, arrest and reversal of the remodeling process
Apoptosis plays a pivotal role in heart failure. Although the apoptotic cascade is initiated, it does not complete in heart failure ('
apoptosis interruptus
')
Interrupted apoptosis reconfirms that heart failure could often be a reversible disease state, and offers an attractive target for management</description><identifier>ISSN: 1743-4297</identifier><identifier>ISSN: 1759-5002</identifier><identifier>EISSN: 1743-4300</identifier><identifier>EISSN: 1759-5010</identifier><identifier>DOI: 10.1038/ncpcardio0710</identifier><identifier>PMID: 17122801</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Apoptosis - drug effects ; Cardiac Imaging ; Cardiac Output, Low - metabolism ; Cardiac Output, Low - pathology ; Cardiac Output, Low - physiopathology ; Cardiac Surgery ; Cardiology ; Caspases - metabolism ; Cytochromes c - metabolism ; Energy Metabolism - drug effects ; Enzyme Activation - drug effects ; Humans ; Medicine ; Medicine & Public Health ; Mitochondria, Heart - drug effects ; Mitochondria, Heart - metabolism ; Myocardial Contraction - drug effects ; Myocardium - metabolism ; Myocardium - pathology ; Protease Inhibitors - pharmacology ; review-article ; Ventricular Remodeling - drug effects</subject><ispartof>Nature clinical practice cardiovascular medicine, 2006-12, Vol.3 (12), p.681-688</ispartof><rights>Springer Nature Limited 2006</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-577b5dd5ba448cd7d06bf35a2c21b319aad562ce9da30121379cd12bb9d539953</citedby><cites>FETCH-LOGICAL-c491t-577b5dd5ba448cd7d06bf35a2c21b319aad562ce9da30121379cd12bb9d539953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17122801$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Narula, Jagat</creatorcontrib><creatorcontrib>Haider, Nezam</creatorcontrib><creatorcontrib>Arbustini, Eloisa</creatorcontrib><creatorcontrib>Chandrashekhar, Y</creatorcontrib><title>Mechanisms of Disease: apoptosis in heart failure-seeing hope in death</title><title>Nature clinical practice cardiovascular medicine</title><addtitle>Nat Rev Cardiol</addtitle><addtitle>Nat Clin Pract Cardiovasc Med</addtitle><description>The loss of cardiomyocytes in failing or cardiomyopathic hearts is gradual and not accompanied by inflammation or major histomorphologic deformity. Apoptosis, therefore, seems to be the most logical mechanism of cell death. In this Review, Narula
et al
. discuss the role of apoptosis in systolic dysfunction and heart failure, and in the development of novel strategies for the management of heart failure.
Apoptosis or programmed cell death is an evolutionarily conserved process of cell death, wherein cells die without provoking significant inflammatory response. There is convincing evidence that apoptosis contributes to the progression of heart failure. Apoptosis occurs through a cascade of subcellular events including cytochrome
c
release into the cytoplasm and activation of proteolytic caspases. Activated caspases lead to fragmentation of cytoplasmic proteins, including contractile apparatus, to a variable extent. It is proposed that the release of cytochrome
c
from mitochondria and contractile protein loss in living heart muscle cells contributes to systolic dysfunction. Interestingly, despite extensive changes in the cytoplasm, nuclear damage, which is the final event in apoptosis, is rather infrequent in the failing heart. Since the nucleus remains unaffected and the genetic blueprint intact in cells with interrupted apoptosis, these heart muscle cells might be amenable to cytoplasmic reconstitution. This process of '
apoptosis interruptus
' could allow development of novel strategies to reverse or attenuate heart failure.
Key Points
Heart failure is a major cardiovascular health problem worldwide
Heart failure is characterized by inexorable progression of systolic dysfunction through the process of adverse cardiac remodeling even after the initial, causal injury has abated
Understanding the pathophysiological substrates of cardiac remodeling can help in the development of novel strategies for prevention, arrest and reversal of the remodeling process
Apoptosis plays a pivotal role in heart failure. Although the apoptotic cascade is initiated, it does not complete in heart failure ('
apoptosis interruptus
')
Interrupted apoptosis reconfirms that heart failure could often be a reversible disease state, and offers an attractive target for management</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Cardiac Imaging</subject><subject>Cardiac Output, Low - metabolism</subject><subject>Cardiac Output, Low - pathology</subject><subject>Cardiac Output, Low - physiopathology</subject><subject>Cardiac Surgery</subject><subject>Cardiology</subject><subject>Caspases - metabolism</subject><subject>Cytochromes c - metabolism</subject><subject>Energy Metabolism - drug effects</subject><subject>Enzyme Activation - drug effects</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mitochondria, Heart - drug effects</subject><subject>Mitochondria, Heart - metabolism</subject><subject>Myocardial Contraction - drug effects</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Protease Inhibitors - pharmacology</subject><subject>review-article</subject><subject>Ventricular Remodeling - drug effects</subject><issn>1743-4297</issn><issn>1759-5002</issn><issn>1743-4300</issn><issn>1759-5010</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kc1r3DAQxUVpyVdz7LUYCrk51Ui2ZfUWNh8NJOTSns1YGu8q2JIr2Yf89_Gym6YphDlomPnN44nH2Bfg58Bl_d2b0WC0LnAF_AM7AlXIvJCcf3zphVaH7DilR86lUrI-YIegQIiawxG7viezQe_SkLLQZZcuESb6keEYxikklzLnsw1hnLIOXT9HyhOR8-tsE0baLi3htPnMPnXYJzrdvyfs9_XVr9XP_O7h5nZ1cZebQsOUl0q1pbVli0VRG6ssr9pOliiMgFaCRrRlJQxpi5KDAKm0sSDaVttSal3KE3a20x1j-DNTmprBJUN9j57CnJqqBlXxQizgt__AxzBHv3hrQNWF0gpgS53vqDX21DjfhSmiWcrS4Ezw1LllfgF1rURVCbUc5LsDE0NKkbpmjG7A-NQAb7Z5NG_yWPivextzO5B9pfcBvDpIy8qvKf7j8x3F_cc8TksafxXfUs-Ko6M2</recordid><startdate>20061201</startdate><enddate>20061201</enddate><creator>Narula, Jagat</creator><creator>Haider, Nezam</creator><creator>Arbustini, Eloisa</creator><creator>Chandrashekhar, Y</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20061201</creationdate><title>Mechanisms of Disease: apoptosis in heart failure-seeing hope in death</title><author>Narula, Jagat ; Haider, Nezam ; Arbustini, Eloisa ; Chandrashekhar, Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-577b5dd5ba448cd7d06bf35a2c21b319aad562ce9da30121379cd12bb9d539953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Cardiac Imaging</topic><topic>Cardiac Output, Low - metabolism</topic><topic>Cardiac Output, Low - pathology</topic><topic>Cardiac Output, Low - physiopathology</topic><topic>Cardiac Surgery</topic><topic>Cardiology</topic><topic>Caspases - metabolism</topic><topic>Cytochromes c - metabolism</topic><topic>Energy Metabolism - drug effects</topic><topic>Enzyme Activation - drug effects</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mitochondria, Heart - drug effects</topic><topic>Mitochondria, Heart - metabolism</topic><topic>Myocardial Contraction - drug effects</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Protease Inhibitors - pharmacology</topic><topic>review-article</topic><topic>Ventricular Remodeling - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Narula, Jagat</creatorcontrib><creatorcontrib>Haider, Nezam</creatorcontrib><creatorcontrib>Arbustini, Eloisa</creatorcontrib><creatorcontrib>Chandrashekhar, Y</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Nature clinical practice cardiovascular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Narula, Jagat</au><au>Haider, Nezam</au><au>Arbustini, Eloisa</au><au>Chandrashekhar, Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms of Disease: apoptosis in heart failure-seeing hope in death</atitle><jtitle>Nature clinical practice cardiovascular medicine</jtitle><stitle>Nat Rev Cardiol</stitle><addtitle>Nat Clin Pract Cardiovasc Med</addtitle><date>2006-12-01</date><risdate>2006</risdate><volume>3</volume><issue>12</issue><spage>681</spage><epage>688</epage><pages>681-688</pages><issn>1743-4297</issn><issn>1759-5002</issn><eissn>1743-4300</eissn><eissn>1759-5010</eissn><abstract>The loss of cardiomyocytes in failing or cardiomyopathic hearts is gradual and not accompanied by inflammation or major histomorphologic deformity. Apoptosis, therefore, seems to be the most logical mechanism of cell death. In this Review, Narula
et al
. discuss the role of apoptosis in systolic dysfunction and heart failure, and in the development of novel strategies for the management of heart failure.
Apoptosis or programmed cell death is an evolutionarily conserved process of cell death, wherein cells die without provoking significant inflammatory response. There is convincing evidence that apoptosis contributes to the progression of heart failure. Apoptosis occurs through a cascade of subcellular events including cytochrome
c
release into the cytoplasm and activation of proteolytic caspases. Activated caspases lead to fragmentation of cytoplasmic proteins, including contractile apparatus, to a variable extent. It is proposed that the release of cytochrome
c
from mitochondria and contractile protein loss in living heart muscle cells contributes to systolic dysfunction. Interestingly, despite extensive changes in the cytoplasm, nuclear damage, which is the final event in apoptosis, is rather infrequent in the failing heart. Since the nucleus remains unaffected and the genetic blueprint intact in cells with interrupted apoptosis, these heart muscle cells might be amenable to cytoplasmic reconstitution. This process of '
apoptosis interruptus
' could allow development of novel strategies to reverse or attenuate heart failure.
Key Points
Heart failure is a major cardiovascular health problem worldwide
Heart failure is characterized by inexorable progression of systolic dysfunction through the process of adverse cardiac remodeling even after the initial, causal injury has abated
Understanding the pathophysiological substrates of cardiac remodeling can help in the development of novel strategies for prevention, arrest and reversal of the remodeling process
Apoptosis plays a pivotal role in heart failure. Although the apoptotic cascade is initiated, it does not complete in heart failure ('
apoptosis interruptus
')
Interrupted apoptosis reconfirms that heart failure could often be a reversible disease state, and offers an attractive target for management</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17122801</pmid><doi>10.1038/ncpcardio0710</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Apoptosis - drug effects Cardiac Imaging Cardiac Output, Low - metabolism Cardiac Output, Low - pathology Cardiac Output, Low - physiopathology Cardiac Surgery Cardiology Caspases - metabolism Cytochromes c - metabolism Energy Metabolism - drug effects Enzyme Activation - drug effects Humans Medicine Medicine & Public Health Mitochondria, Heart - drug effects Mitochondria, Heart - metabolism Myocardial Contraction - drug effects Myocardium - metabolism Myocardium - pathology Protease Inhibitors - pharmacology review-article Ventricular Remodeling - drug effects |
title | Mechanisms of Disease: apoptosis in heart failure-seeing hope in death |
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