Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart
ABSTRACT In animal models of lipotoxicity, accumulation of triglycerides within cardiomyocytes is associated with contractile dysfunction. However, whether intramyocardial lipid deposition is a feature of human heart failure remains to be established. We hypothesized that intramyocardial lipid accum...
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| creator | Sharma, Saumya Adrogue, Julia V. Golfman, Leonard Uray, Ivan Lemm, John Youker, Keith Noon, George P. Frazier, O. H. Taegtmeyer, Heinrich |
| description | ABSTRACT
In animal models of lipotoxicity, accumulation of triglycerides within cardiomyocytes is associated with contractile dysfunction. However, whether intramyocardial lipid deposition is a feature of human heart failure remains to be established. We hypothesized that intramyocardial lipid accumulation is a common feature of non‐ischemic heart failure and is associated with changes in gene expression similar to those found in an animal model of lipotoxicity. Intramyocardial lipid staining with oil red O and gene expression analysis was performed on heart tissue from 27 patients (9 female) with non‐ischemic heart failure. We determined intramyocardial lipid, gene expression, and contractile function in hearts from 6 Zucker diabetic fatty (ZDF) and 6 Zucker lean (ZL) rats. Intramyocardial lipid overload was present in 30% of non‐ischemic failing hearts. The highest levels of lipid staining were observed in patients with diabetes and obesity (BMI>30). Intramyocardial lipid deposition was associated with an up‐regulation of peroxisome proliferator‐activated receptor a (PPARα) ‐regulated genes, myosin heavy chain β (MHC‐β), and tumor necrosis factor α (TNF‐α). Intramyocardial lipid overload in the hearts of ZDF rats was associated with contractile dysfunction and changes in gene expression similar to changes found in failing human hearts with lipid overload. Our findings identify a subgroup of patients with heart failure and severe metabolic dysregulation characterized by intramyocardial triglyceride overload and changes in gene expression that are associated with contractile dysfunction.—Sharma, S., Adrogue, J. V., Golfman, L., Uray, I., Lemm, J., Youker, K., Noon, G. P., Frazier, O. H., Taegtmeyer, H. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J. 18, 1692–1700 (2004) |
| doi_str_mv | 10.1096/fj.04-2263com |
| format | Article |
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In animal models of lipotoxicity, accumulation of triglycerides within cardiomyocytes is associated with contractile dysfunction. However, whether intramyocardial lipid deposition is a feature of human heart failure remains to be established. We hypothesized that intramyocardial lipid accumulation is a common feature of non‐ischemic heart failure and is associated with changes in gene expression similar to those found in an animal model of lipotoxicity. Intramyocardial lipid staining with oil red O and gene expression analysis was performed on heart tissue from 27 patients (9 female) with non‐ischemic heart failure. We determined intramyocardial lipid, gene expression, and contractile function in hearts from 6 Zucker diabetic fatty (ZDF) and 6 Zucker lean (ZL) rats. Intramyocardial lipid overload was present in 30% of non‐ischemic failing hearts. The highest levels of lipid staining were observed in patients with diabetes and obesity (BMI>30). Intramyocardial lipid deposition was associated with an up‐regulation of peroxisome proliferator‐activated receptor a (PPARα) ‐regulated genes, myosin heavy chain β (MHC‐β), and tumor necrosis factor α (TNF‐α). Intramyocardial lipid overload in the hearts of ZDF rats was associated with contractile dysfunction and changes in gene expression similar to changes found in failing human hearts with lipid overload. Our findings identify a subgroup of patients with heart failure and severe metabolic dysregulation characterized by intramyocardial triglyceride overload and changes in gene expression that are associated with contractile dysfunction.—Sharma, S., Adrogue, J. V., Golfman, L., Uray, I., Lemm, J., Youker, K., Noon, G. P., Frazier, O. H., Taegtmeyer, H. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J. 18, 1692–1700 (2004)</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.04-2263com</identifier><identifier>PMID: 15522914</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Aged ; Animals ; Cardiac Output, Low - complications ; Cardiac Output, Low - metabolism ; Cardiac Output, Low - physiopathology ; contractile dysfunction ; Diabetes Mellitus, Type 2 - complications ; Disease Models, Animal ; Female ; Gene Expression ; Humans ; lipotoxicity ; Male ; Middle Aged ; Myocardium - metabolism ; Myosins - biosynthesis ; Myosins - genetics ; non‐ischemic heart failure ; Obesity - complications ; Rats ; Rats, Zucker ; Sarcomeres - metabolism ; triglyceride accumulation ; Triglycerides - metabolism ; Tumor Necrosis Factor-alpha - biosynthesis ; Tumor Necrosis Factor-alpha - genetics</subject><ispartof>The FASEB journal, 2004-11, Vol.18 (14), p.1692-1700</ispartof><rights>FASEB</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c469M-2bfd6d7d11f609cbdd8a9af77991971e508d5cbe1e128e1431f52433b6445e673</citedby><cites>FETCH-LOGICAL-c469M-2bfd6d7d11f609cbdd8a9af77991971e508d5cbe1e128e1431f52433b6445e673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.04-2263com$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.04-2263com$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15522914$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sharma, Saumya</creatorcontrib><creatorcontrib>Adrogue, Julia V.</creatorcontrib><creatorcontrib>Golfman, Leonard</creatorcontrib><creatorcontrib>Uray, Ivan</creatorcontrib><creatorcontrib>Lemm, John</creatorcontrib><creatorcontrib>Youker, Keith</creatorcontrib><creatorcontrib>Noon, George P.</creatorcontrib><creatorcontrib>Frazier, O. H.</creatorcontrib><creatorcontrib>Taegtmeyer, Heinrich</creatorcontrib><title>Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>ABSTRACT
In animal models of lipotoxicity, accumulation of triglycerides within cardiomyocytes is associated with contractile dysfunction. However, whether intramyocardial lipid deposition is a feature of human heart failure remains to be established. We hypothesized that intramyocardial lipid accumulation is a common feature of non‐ischemic heart failure and is associated with changes in gene expression similar to those found in an animal model of lipotoxicity. Intramyocardial lipid staining with oil red O and gene expression analysis was performed on heart tissue from 27 patients (9 female) with non‐ischemic heart failure. We determined intramyocardial lipid, gene expression, and contractile function in hearts from 6 Zucker diabetic fatty (ZDF) and 6 Zucker lean (ZL) rats. Intramyocardial lipid overload was present in 30% of non‐ischemic failing hearts. The highest levels of lipid staining were observed in patients with diabetes and obesity (BMI>30). Intramyocardial lipid deposition was associated with an up‐regulation of peroxisome proliferator‐activated receptor a (PPARα) ‐regulated genes, myosin heavy chain β (MHC‐β), and tumor necrosis factor α (TNF‐α). Intramyocardial lipid overload in the hearts of ZDF rats was associated with contractile dysfunction and changes in gene expression similar to changes found in failing human hearts with lipid overload. Our findings identify a subgroup of patients with heart failure and severe metabolic dysregulation characterized by intramyocardial triglyceride overload and changes in gene expression that are associated with contractile dysfunction.—Sharma, S., Adrogue, J. V., Golfman, L., Uray, I., Lemm, J., Youker, K., Noon, G. P., Frazier, O. H., Taegtmeyer, H. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J. 18, 1692–1700 (2004)</description><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Cardiac Output, Low - complications</subject><subject>Cardiac Output, Low - metabolism</subject><subject>Cardiac Output, Low - physiopathology</subject><subject>contractile dysfunction</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>lipotoxicity</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myocardium - metabolism</subject><subject>Myosins - biosynthesis</subject><subject>Myosins - genetics</subject><subject>non‐ischemic heart failure</subject><subject>Obesity - complications</subject><subject>Rats</subject><subject>Rats, Zucker</subject><subject>Sarcomeres - metabolism</subject><subject>triglyceride accumulation</subject><subject>Triglycerides - metabolism</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0LFv1DAUBnCrKqLXwti18tQtxc92nLgbnDha1KoDMFuO_dzzyUmudiK4_54rdxIbTE9P-n3f8BFyCewGmFYfwuaGyYpzJdzYn5AF1IJVqlXslCxYq3mllGjPyHkpG8YYMFBvyRnUNeca5IKY-2HKtt-NzmYfbaIpbqOn1rm5n5Od4jjQONBpjTTYmOLwTNdzbwe6RpsnmrFg3yUsf8Q-O07jr-hottNBvCNvgk0F3x_vBfmx-vx9eVc9PH25X358qJxU-rHiXfDKNx4gKKZd531rtQ1NozXoBrBmra9dh4DAWwQpINRcCtEpKWtUjbgg14febR5fZiyT6WNxmJIdcJyLUQ0TtdLtfyE0jQLQbA-rA3R5LCVjMNsce5t3Bph5nd6EjWHSHKff-6tj8dz16P_q49Z7cHsAP2PC3b_bzOrbJ776yuTrv3x6FL8B1aaSzg</recordid><startdate>200411</startdate><enddate>200411</enddate><creator>Sharma, Saumya</creator><creator>Adrogue, Julia V.</creator><creator>Golfman, Leonard</creator><creator>Uray, Ivan</creator><creator>Lemm, John</creator><creator>Youker, Keith</creator><creator>Noon, George P.</creator><creator>Frazier, O. 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In animal models of lipotoxicity, accumulation of triglycerides within cardiomyocytes is associated with contractile dysfunction. However, whether intramyocardial lipid deposition is a feature of human heart failure remains to be established. We hypothesized that intramyocardial lipid accumulation is a common feature of non‐ischemic heart failure and is associated with changes in gene expression similar to those found in an animal model of lipotoxicity. Intramyocardial lipid staining with oil red O and gene expression analysis was performed on heart tissue from 27 patients (9 female) with non‐ischemic heart failure. We determined intramyocardial lipid, gene expression, and contractile function in hearts from 6 Zucker diabetic fatty (ZDF) and 6 Zucker lean (ZL) rats. Intramyocardial lipid overload was present in 30% of non‐ischemic failing hearts. The highest levels of lipid staining were observed in patients with diabetes and obesity (BMI>30). Intramyocardial lipid deposition was associated with an up‐regulation of peroxisome proliferator‐activated receptor a (PPARα) ‐regulated genes, myosin heavy chain β (MHC‐β), and tumor necrosis factor α (TNF‐α). Intramyocardial lipid overload in the hearts of ZDF rats was associated with contractile dysfunction and changes in gene expression similar to changes found in failing human hearts with lipid overload. Our findings identify a subgroup of patients with heart failure and severe metabolic dysregulation characterized by intramyocardial triglyceride overload and changes in gene expression that are associated with contractile dysfunction.—Sharma, S., Adrogue, J. V., Golfman, L., Uray, I., Lemm, J., Youker, K., Noon, G. P., Frazier, O. H., Taegtmeyer, H. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J. 18, 1692–1700 (2004)</abstract><cop>United States</cop><pmid>15522914</pmid><doi>10.1096/fj.04-2263com</doi><tpages>9</tpages></addata></record> |
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| subjects | Adult Aged Animals Cardiac Output, Low - complications Cardiac Output, Low - metabolism Cardiac Output, Low - physiopathology contractile dysfunction Diabetes Mellitus, Type 2 - complications Disease Models, Animal Female Gene Expression Humans lipotoxicity Male Middle Aged Myocardium - metabolism Myosins - biosynthesis Myosins - genetics non‐ischemic heart failure Obesity - complications Rats Rats, Zucker Sarcomeres - metabolism triglyceride accumulation Triglycerides - metabolism Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - genetics |
| title | Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart |
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