Pub Date : 2024-10-21DOI: 10.1038/s44161-024-00553-6
Farid F. Kadyrov, Andrew L. Koenig, Junedh M. Amrute, Hao Dun, Wenjun Li, Carla J. Weinheimer, Jessica M. Nigro, Attila Kovacs, Andrea L. Bredemeyer, Steven Yang, Shibali Das, Vinay R. Penna, Alekhya Parvathaneni, Lulu Lai, Niklas Hartmann, Benjamin J. Kopecky, Daniel Kreisel, Kory J. Lavine
Myocardial infarction initiates cardiac remodeling and is central to heart failure pathogenesis. Following myocardial ischemia–reperfusion injury, monocytes enter the heart and differentiate into diverse subpopulations of macrophages. Here we show that deletion of Hif1α, a hypoxia response transcription factor, in resident cardiac macrophages led to increased remodeling and overrepresentation of macrophages expressing arginase 1 (Arg1). Arg1+ macrophages displayed an inflammatory gene signature and may represent an intermediate state of monocyte differentiation. Lineage tracing of Arg1+ macrophages revealed a monocyte differentiation trajectory consisting of multiple transcriptionally distinct states. We further showed that deletion of Hif1α in resident cardiac macrophages resulted in arrested progression through this trajectory and accumulation of an inflammatory intermediate state marked by persistent Arg1 expression. Depletion of the Arg1+ trajectory accelerated cardiac remodeling following ischemic injury. Our findings unveil distinct trajectories of monocyte differentiation and identify hypoxia sensing as an important determinant of monocyte differentiation following myocardial infarction. Kadyrov et al. reveal that the hypoxia sensing through HIF1A is an important regulator of monocyte-derived macrophage differentiation, which determines the extent of inflammation and cardiac remodeling after injury.
{"title":"Hypoxia sensing in resident cardiac macrophages regulates monocyte fate specification following ischemic heart injury","authors":"Farid F. Kadyrov, Andrew L. Koenig, Junedh M. Amrute, Hao Dun, Wenjun Li, Carla J. Weinheimer, Jessica M. Nigro, Attila Kovacs, Andrea L. Bredemeyer, Steven Yang, Shibali Das, Vinay R. Penna, Alekhya Parvathaneni, Lulu Lai, Niklas Hartmann, Benjamin J. Kopecky, Daniel Kreisel, Kory J. Lavine","doi":"10.1038/s44161-024-00553-6","DOIUrl":"10.1038/s44161-024-00553-6","url":null,"abstract":"Myocardial infarction initiates cardiac remodeling and is central to heart failure pathogenesis. Following myocardial ischemia–reperfusion injury, monocytes enter the heart and differentiate into diverse subpopulations of macrophages. Here we show that deletion of Hif1α, a hypoxia response transcription factor, in resident cardiac macrophages led to increased remodeling and overrepresentation of macrophages expressing arginase 1 (Arg1). Arg1+ macrophages displayed an inflammatory gene signature and may represent an intermediate state of monocyte differentiation. Lineage tracing of Arg1+ macrophages revealed a monocyte differentiation trajectory consisting of multiple transcriptionally distinct states. We further showed that deletion of Hif1α in resident cardiac macrophages resulted in arrested progression through this trajectory and accumulation of an inflammatory intermediate state marked by persistent Arg1 expression. Depletion of the Arg1+ trajectory accelerated cardiac remodeling following ischemic injury. Our findings unveil distinct trajectories of monocyte differentiation and identify hypoxia sensing as an important determinant of monocyte differentiation following myocardial infarction. Kadyrov et al. reveal that the hypoxia sensing through HIF1A is an important regulator of monocyte-derived macrophage differentiation, which determines the extent of inflammation and cardiac remodeling after injury.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 11","pages":"1337-1355"},"PeriodicalIF":9.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1038/s44161-024-00543-8
Dilip Thomas, Chikage Noishiki, Sadhana Gaddam, David Wu, Amit Manhas, Yu Liu, Dipti Tripathi, Nimish Kathale, Shaunak S. Adkar, Jaishree Garhyan, Chun Liu, Baohui Xu, Elsie G. Ross, Ronald L. Dalman, Kevin C. Wang, Anthony E. Oro, Karim Sallam, Jason T. Lee, Joseph C. Wu, Nazish Sayed
Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to ‘phenotype switching’ and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID. Thomas, Noishiki, Gaddam et al. used thrombotic vascular tissues and iPSC-derived cardiac organoids to show that COVID-19-induced endotheliitis and cytokine release disrupt endothelial–cardiomyocyte crosstalk and contribute to cardiac dysfunction in long COVID.
{"title":"CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID","authors":"Dilip Thomas, Chikage Noishiki, Sadhana Gaddam, David Wu, Amit Manhas, Yu Liu, Dipti Tripathi, Nimish Kathale, Shaunak S. Adkar, Jaishree Garhyan, Chun Liu, Baohui Xu, Elsie G. Ross, Ronald L. Dalman, Kevin C. Wang, Anthony E. Oro, Karim Sallam, Jason T. Lee, Joseph C. Wu, Nazish Sayed","doi":"10.1038/s44161-024-00543-8","DOIUrl":"10.1038/s44161-024-00543-8","url":null,"abstract":"Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to ‘phenotype switching’ and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID. Thomas, Noishiki, Gaddam et al. used thrombotic vascular tissues and iPSC-derived cardiac organoids to show that COVID-19-induced endotheliitis and cytokine release disrupt endothelial–cardiomyocyte crosstalk and contribute to cardiac dysfunction in long COVID.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1249-1265"},"PeriodicalIF":9.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1038/s44161-024-00551-8
Simon R. Foster, James E. Hudson
The molecular mechanisms that underpin the multi-organ dysfunction in long COVID are unknown, particularly within the cardiovascular system. Research finds a critical role for endothelial responses and signaling in driving dysfunction.
{"title":"Endothelial cells as paracrine mediators of long COVID","authors":"Simon R. Foster, James E. Hudson","doi":"10.1038/s44161-024-00551-8","DOIUrl":"10.1038/s44161-024-00551-8","url":null,"abstract":"The molecular mechanisms that underpin the multi-organ dysfunction in long COVID are unknown, particularly within the cardiovascular system. Research finds a critical role for endothelial responses and signaling in driving dysfunction.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1181-1183"},"PeriodicalIF":9.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-07DOI: 10.1038/s44161-024-00547-4
Inês Cebola, Graeme M. Birdsey, Anna M. Randi
In-depth in vivo and in vitro functional analyses, along with a series of genomic assays, reveal RNF20 as a molecular rheostat controlling the balance between endothelial VEGF and Notch signaling during sprouting angiogenesis.
{"title":"Transcriptional pausing as a molecular mechanism of sprouting angiogenesis","authors":"Inês Cebola, Graeme M. Birdsey, Anna M. Randi","doi":"10.1038/s44161-024-00547-4","DOIUrl":"10.1038/s44161-024-00547-4","url":null,"abstract":"In-depth in vivo and in vitro functional analyses, along with a series of genomic assays, reveal RNF20 as a molecular rheostat controlling the balance between endothelial VEGF and Notch signaling during sprouting angiogenesis.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1184-1186"},"PeriodicalIF":9.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1038/s44161-024-00552-7
Analyses of transcription and translation identify newly evolved genes and translated sequences (open reading frames) unique to hearts from human and non-human primates, suggesting that these genetic innovations might influence cardiac development and disease.
{"title":"Evolution of cardiac genomic elements in humans and non-human primates","authors":"","doi":"10.1038/s44161-024-00552-7","DOIUrl":"10.1038/s44161-024-00552-7","url":null,"abstract":"Analyses of transcription and translation identify newly evolved genes and translated sequences (open reading frames) unique to hearts from human and non-human primates, suggesting that these genetic innovations might influence cardiac development and disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1187-1188"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.1038/s44161-024-00546-5
Nalan Tetik-Elsherbiny, Adel Elsherbiny, Aadhyaa Setya, Johannes Gahn, Yongqin Tang, Purnima Gupta, Yanliang Dou, Heike Serke, Thomas Wieland, Alexandre Dubrac, Joerg Heineke, Michael Potente, Julio Cordero, Roxana Ola, Gergana Dobreva
Signal-responsive gene expression is essential for vascular development, yet the mechanisms integrating signaling inputs with transcriptional activities are largely unknown. Here we show that RNF20, the primary E3 ubiquitin ligase for histone H2B, plays a multifaceted role in sprouting angiogenesis. RNF20 mediates RNA polymerase (Pol II) promoter-proximal pausing at genes highly paused in endothelial cells, involved in VEGFA signaling, stress response, cell cycle control and mRNA splicing. It also orchestrates large-scale mRNA processing events that alter the bioavailability and function of critical pro-angiogenic factors, such as VEGFA. Mechanistically, RNF20 restricts ERG-dependent Pol II pause release at highly paused genes while binding to Notch1 to promote H2B monoubiquitination at Notch target genes and Notch-dependent gene expression. This balance is crucial, as loss of Rnf20 leads to uncontrolled tip cell specification. Our findings highlight the pivotal role of RNF20 in regulating VEGF–Notch signaling circuits during vessel growth, underscoring its potential for therapeutic modulation of angiogenesis. Tetik-Elsherbiny et al. demonstrate that the E3 ubiquitin ligase RNF20 mediates RNA polymerase II promoter-proximal pausing and alternative splicing, regulating the bioavailability and signaling of pro-angiogenic factors and angiogenesis.
{"title":"RNF20-mediated transcriptional pausing and VEGFA splicing orchestrate vessel growth","authors":"Nalan Tetik-Elsherbiny, Adel Elsherbiny, Aadhyaa Setya, Johannes Gahn, Yongqin Tang, Purnima Gupta, Yanliang Dou, Heike Serke, Thomas Wieland, Alexandre Dubrac, Joerg Heineke, Michael Potente, Julio Cordero, Roxana Ola, Gergana Dobreva","doi":"10.1038/s44161-024-00546-5","DOIUrl":"10.1038/s44161-024-00546-5","url":null,"abstract":"Signal-responsive gene expression is essential for vascular development, yet the mechanisms integrating signaling inputs with transcriptional activities are largely unknown. Here we show that RNF20, the primary E3 ubiquitin ligase for histone H2B, plays a multifaceted role in sprouting angiogenesis. RNF20 mediates RNA polymerase (Pol II) promoter-proximal pausing at genes highly paused in endothelial cells, involved in VEGFA signaling, stress response, cell cycle control and mRNA splicing. It also orchestrates large-scale mRNA processing events that alter the bioavailability and function of critical pro-angiogenic factors, such as VEGFA. Mechanistically, RNF20 restricts ERG-dependent Pol II pause release at highly paused genes while binding to Notch1 to promote H2B monoubiquitination at Notch target genes and Notch-dependent gene expression. This balance is crucial, as loss of Rnf20 leads to uncontrolled tip cell specification. Our findings highlight the pivotal role of RNF20 in regulating VEGF–Notch signaling circuits during vessel growth, underscoring its potential for therapeutic modulation of angiogenesis. Tetik-Elsherbiny et al. demonstrate that the E3 ubiquitin ligase RNF20 mediates RNA polymerase II promoter-proximal pausing and alternative splicing, regulating the bioavailability and signaling of pro-angiogenic factors and angiogenesis.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1199-1216"},"PeriodicalIF":9.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00546-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.1038/s44161-024-00545-6
Lars Lind, Mohsen Mazidi, Robert Clarke, Derrick A. Bennett, Rui Zheng
Several large-scale studies have measured plasma levels of the proteome in individuals with cardiovascular diseases (CVDs)1–7. However, since the majority of such proteins are interrelated2, it is difficult for observational studies to distinguish which proteins are likely to be of etiological relevance. Here we evaluate whether plasma levels of 2,919 proteins measured in 52,164 UK Biobank participants are associated with incident myocardial infarction, ischemic stroke or heart failure. Of those proteins, 126 were associated with all three CVD outcomes and 118 were associated with at least one CVD in the China Kadoorie Biobank. Mendelian randomization and colocalization analyses indicated that genetically determined levels of 47 and 18 proteins, respectively, were associated with CVDs, including FGF5, PROCR and FURIN. While the majority of protein–CVD observational associations were noncausal, these three proteins showed evidence to support potential causality and are therefore promising targets for drug treatment for CVD outcomes. Lind et al. investigate the causal relationship between plasma proteins and cardiovascular disease outcomes in patients of European and Chinese descent, identifying FGF5, PROCR and FURIN as promising targets for the development of new drugs.
{"title":"Measured and genetically predicted protein levels and cardiovascular diseases in UK Biobank and China Kadoorie Biobank","authors":"Lars Lind, Mohsen Mazidi, Robert Clarke, Derrick A. Bennett, Rui Zheng","doi":"10.1038/s44161-024-00545-6","DOIUrl":"10.1038/s44161-024-00545-6","url":null,"abstract":"Several large-scale studies have measured plasma levels of the proteome in individuals with cardiovascular diseases (CVDs)1–7. However, since the majority of such proteins are interrelated2, it is difficult for observational studies to distinguish which proteins are likely to be of etiological relevance. Here we evaluate whether plasma levels of 2,919 proteins measured in 52,164 UK Biobank participants are associated with incident myocardial infarction, ischemic stroke or heart failure. Of those proteins, 126 were associated with all three CVD outcomes and 118 were associated with at least one CVD in the China Kadoorie Biobank. Mendelian randomization and colocalization analyses indicated that genetically determined levels of 47 and 18 proteins, respectively, were associated with CVDs, including FGF5, PROCR and FURIN. While the majority of protein–CVD observational associations were noncausal, these three proteins showed evidence to support potential causality and are therefore promising targets for drug treatment for CVD outcomes. Lind et al. investigate the causal relationship between plasma proteins and cardiovascular disease outcomes in patients of European and Chinese descent, identifying FGF5, PROCR and FURIN as promising targets for the development of new drugs.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1189-1198"},"PeriodicalIF":9.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00545-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1038/s44161-024-00544-7
Jorge Ruiz-Orera, Duncan C. Miller, Johannes Greiner, Carolin Genehr, Aliki Grammatikaki, Susanne Blachut, Jeanne Mbebi, Giannino Patone, Anna Myronova, Eleonora Adami, Nikita Dewani, Ning Liang, Oliver Hummel, Michael B. Muecke, Thomas B. Hildebrandt, Guido Fritsch, Lisa Schrade, Wolfram H. Zimmermann, Ivanela Kondova, Sebastian Diecke, Sebastiaan van Heesch, Norbert Hübner
Evolutionary innovations can be driven by changes in the rates of RNA translation and the emergence of new genes and small open reading frames (sORFs). In this study, we characterized the transcriptional and translational landscape of the hearts of four primate and two rodent species through integrative ribosome and transcriptomic profiling, including adult left ventricle tissues and induced pluripotent stem cell-derived cardiomyocyte cell cultures. We show here that the translational efficiencies of subunits of the mitochondrial oxidative phosphorylation chain complexes IV and V evolved rapidly across mammalian evolution. Moreover, we discovered hundreds of species-specific and lineage-specific genomic innovations that emerged during primate evolution in the heart, including 551 genes, 504 sORFs and 76 evolutionarily conserved genes displaying human-specific cardiac-enriched expression. Overall, our work describes the evolutionary processes and mechanisms that have shaped cardiac transcription and translation in recent primate evolution and sheds light on how these can contribute to cardiac development and disease. Ruiz-Orera et al. used comparative transcriptomics and translatomics to analyze the cardiac evolution in primates and discovered species-specific and lineage-specific genomic innovations that might contribute to cardiac development and disease.
RNA翻译速率的变化以及新基因和小开放阅读框（sORF）的出现可以推动进化创新。在这项研究中，我们通过核糖体和转录组综合分析，包括成人左心室组织和诱导多能干细胞衍生的心肌细胞培养物，描述了四种灵长类动物和两种啮齿类动物心脏的转录和翻译情况。我们在这里发现，线粒体氧化磷酸化链复合物 IV 和 V 亚基的翻译效率在哺乳动物进化过程中迅速进化。此外，我们还发现了灵长类动物心脏进化过程中出现的数百个物种特异性和品系特异性基因组创新，其中包括 551 个基因、504 个 sORF 和 76 个进化保守基因，这些基因显示出人类特异性的心脏丰富表达。总之，我们的工作描述了近代灵长类动物进化过程中形成心脏转录和翻译的进化过程和机制，并揭示了这些过程和机制如何促进心脏发育和疾病的发生。
{"title":"Evolution of translational control and the emergence of genes and open reading frames in human and non-human primate hearts","authors":"Jorge Ruiz-Orera, Duncan C. Miller, Johannes Greiner, Carolin Genehr, Aliki Grammatikaki, Susanne Blachut, Jeanne Mbebi, Giannino Patone, Anna Myronova, Eleonora Adami, Nikita Dewani, Ning Liang, Oliver Hummel, Michael B. Muecke, Thomas B. Hildebrandt, Guido Fritsch, Lisa Schrade, Wolfram H. Zimmermann, Ivanela Kondova, Sebastian Diecke, Sebastiaan van Heesch, Norbert Hübner","doi":"10.1038/s44161-024-00544-7","DOIUrl":"10.1038/s44161-024-00544-7","url":null,"abstract":"Evolutionary innovations can be driven by changes in the rates of RNA translation and the emergence of new genes and small open reading frames (sORFs). In this study, we characterized the transcriptional and translational landscape of the hearts of four primate and two rodent species through integrative ribosome and transcriptomic profiling, including adult left ventricle tissues and induced pluripotent stem cell-derived cardiomyocyte cell cultures. We show here that the translational efficiencies of subunits of the mitochondrial oxidative phosphorylation chain complexes IV and V evolved rapidly across mammalian evolution. Moreover, we discovered hundreds of species-specific and lineage-specific genomic innovations that emerged during primate evolution in the heart, including 551 genes, 504 sORFs and 76 evolutionarily conserved genes displaying human-specific cardiac-enriched expression. Overall, our work describes the evolutionary processes and mechanisms that have shaped cardiac transcription and translation in recent primate evolution and sheds light on how these can contribute to cardiac development and disease. Ruiz-Orera et al. used comparative transcriptomics and translatomics to analyze the cardiac evolution in primates and discovered species-specific and lineage-specific genomic innovations that might contribute to cardiac development and disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1217-1235"},"PeriodicalIF":9.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00544-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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