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Long intergenic noncoding RNAs in cardiovascular diseases: Challenges and strategies for physiological studies and translation.

ABSTRACT: Long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as important mediators of many biological processes relevant to human pathophysiologies, including cardiovascular diseases. In vitro studies have provided important knowledge of cellular functions and mechanisms for an increasing number of lincRNAs. Dysregulated lncRNAs have been associated with cell fate programming and development, vascular diseases, atherosclerosis, dyslipidemia and metabolic syndrome, and cardiac pathological hypertrophy. However, functional interrogation of individual lincRNAs in physiological and disease states is largely limited. The complex nature of lincRNA actions and poor species conservation of human lincRNAs pose substantial challenges to physiological studies in animal model systems and in clinical translation. This review summarizes recent findings of specific lincRNA physiological studies, including MALAT1, MeXis, Lnc-DC and others, in the context of cardiovascular diseases, examines complex mechanisms of lincRNA actions, reviews in vivo research strategies to delineate lincRNA functions and highlights challenges and approaches for physiological studies of primate-specific lincRNAs.

SUBMITTER: Zhang X

PROVIDER: S-EPMC7307970 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Long intergenic noncoding RNAs in cardiovascular diseases: Challenges and strategies for physiological studies and translation.

Zhang Xuan X Li Daniel Y DY Reilly Muredach P MP

Atherosclerosis 20180929

Long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as important mediators of many biological processes relevant to human pathophysiologies, including cardiovascular diseases. In vitro studies have provided important knowledge of cellular functions and mechanisms for an increasing number of lincRNAs. Dysregulated lncRNAs have been associated with cell fate programming and development, vascular diseases, atherosclerosis, dyslipidemia and metabolic syndrome, and cardiac pathologi ...[more]

PMID: 30316538

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Project description:ObjectiveTranscriptome profiling of human tissues has revealed thousands of long intergenic noncoding RNAs (lincRNAs) at loci identified through large-scale genome-wide studies for complex cardiometabolic traits. This raises the question of whether genetic variation at nonconserved lincRNAs has any systematic association with complex disease, and if so, how different this pattern is from conserved lincRNAs. We evaluated whether the associations between nonconserved lincRNAs and 8 complex cardiometabolic traits resemble or differ from the pattern of association for conserved lincRNAs. Approach and Results: Our investigation of over 7000 lincRNA annotations from GENCODE Release 33-GRCh38.p13 for complex trait genetic associations leveraged several large, established meta-analyses genome-wide association study summary data resources, including GIANT (Genetic Investigation of Anthropometric Traits), UK Biobank, GLGC (Global Lipids Genetics Consortium), Cardiogram (Coronary Artery Disease Genome Wide Replication and Meta-Analysis), and DIAGRAM (Diabetes Genetics Replication and Meta-Analysis)/DIAMANTE (Diabetes Meta-Analysis of Trans-Ethnic Association Studies). These analyses revealed that (1) nonconserved lincRNAs associate with a range of cardiometabolic traits at a rate that is generally consistent with conserved lincRNAs; (2) these findings persist across different definitions of conservation; and (3) overall across all cardiometabolic traits, approximately one-third of genome-wide association study-associated lincRNAs are nonconserved, and this increases to about two-thirds using a more stringent definition of conservation.ConclusionsThese findings suggest that the traditional notion of conservation driving prioritization for functional and translational follow-up of complex cardiometabolic genomic discoveries may need to be revised in the context of the abundance of nonconserved long noncoding RNAs in the human genome and their apparent predilection to associate with complex cardiometabolic traits.

Dataset Information

Long intergenic noncoding RNAs in cardiovascular diseases: Challenges and strategies for physiological studies and translation.

Publications

Long intergenic noncoding RNAs in cardiovascular diseases: Challenges and strategies for physiological studies and translation.

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