Deletion of type VIII collagen reduces blood pressure, increases carotid artery functional distensibility and promotes elastin deposition

Mohabeer, Amanda L.; Kroetsch, Jeffrey T.; McFadden, Meghan J.; Khosraviani, Negin; Broekelmann, Thomas J.; Hou, Guangpei; Zhang, Hangjun; Zhou, Yuqing; Wang, Minyao; Gramolini, Anthony O.; Mecham, Robert P.; Heximer, Scott P.; Bolz, Steffen‐Sebastian; Bendeck, Michelle P.

doi:10.1016/j.mbplus.2021.100085

Cited by 11 publications

(5 citation statements)

References 55 publications

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“…For Surti, the genes exactly overlapped with that of the Bhadawari breed. Among the reported genes, Collagen VIII ( COL8 ) is reported to play a major role in vascular integrity [ 68 ]. Jaffarabadi carried the longest CNVR on chromosome 14, which was the smallest one among all the breeds (0.246 Mb) contributing only 0.0089% of the genomic size.…”

Section: Resultsmentioning

confidence: 99%

Read-depth based approach on whole genome resequencing data reveals important insights into the copy number variation (CNV) map of major global buffalo breeds

Ahmad,

Chandrababu Shailaja,

Vaishnav

et al. 2023

BMC Genomics

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Background Elucidating genome-wide structural variants including copy number variations (CNVs) have gained increased significance in recent times owing to their contribution to genetic diversity and association with important pathophysiological states. The present study aimed to elucidate the high-resolution CNV map of six different global buffalo breeds using whole genome resequencing data at two coverages (10X and 30X). Post-quality control, the sequence reads were aligned to the latest draft release of the Bubaline genome. The genome-wide CNVs were elucidated using a read-depth approach in CNVnator with different bin sizes. Adjacent CNVs were concatenated into copy number variation regions (CNVRs) in different breeds and their genomic coverage was elucidated. Results Overall, the average size of CNVR was lower at 30X coverage, providing finer details. Most of the CNVRs were either deletion or duplication type while the occurrence of mixed events was lesser in number on a comparative basis in all breeds. The average CNVR size was lower at 30X coverage (0.201 Mb) as compared to 10X (0.013 Mb) with the finest variants in Banni buffaloes. The maximum number of CNVs was observed in Murrah (2627) and Pandharpuri (25,688) at 10X and 30X coverages, respectively. Whereas the minimum number of CNVs were scored in Surti at both coverages (2092 and 17,373). On the other hand, the highest and lowest number of CNVRs were scored in Jaffarabadi (833 and 10,179 events) and Surti (783 and 7553 events) at both coverages. Deletion events overnumbered duplications in all breeds at both coverages. Gene profiling of common overlapped genes and longest CNVRs provided important insights into the evolutionary history of these breeds and indicate the genomic regions under selection in respective breeds. Conclusion The present study is the first of its kind to elucidate the high-resolution CNV map in major buffalo populations using a read-depth approach on whole genome resequencing data. The results revealed important insights into the divergence of major global buffalo breeds along the evolutionary timescale.

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Section: Resultsmentioning

confidence: 99%

Read-depth based approach on whole genome resequencing data reveals important insights into the copy number variation (CNV) map of major global buffalo breeds

Ahmad,

Chandrababu Shailaja,

Vaishnav

et al. 2023

BMC Genomics

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“…These data suggested that in acute LHF of mice, Col 8 promotes myofibroblast differentiation and fibrosis and protects from early mortality and LV dilatation in response to pressure overload (Skrbic et al, 2015). In a recent study, mice lacking Col8 had reduced baseline blood pressure and altered ECM composition of carotid arteries, suggesting that Col 8 negatively regulates elastic fiber formation in the ECM matrix of blood vessels (Mohabeer et al, 2021).…”

Section: Discussionmentioning

confidence: 96%

A common gene signature of the right ventricle in failing rat and human hearts

Jurida

Werner

Knapp

et al. 2023

Preprint

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The molecular mechanisms of progressive right heart failure are incompletely understood. We systematically compared rat models of pulmonary artery or aortic banding to identify the transcriptomic changes that occur over months in the failing right versus left ventricle. Detailed bioinformatics analyses of 181 RNAseq datasets from cardiomyocytes or whole heart samples from these models, led to the identification of gene signatures, protein, and transcription factor networks specific to ventricles, compensated or decompensated disease states and type of heart failure. RNA-FISH approaches confirmed PAB-mediated regulation of key genes and revealed striking, spatially heterogeneous mRNA expression in the heart. Intersection of rat PAB-specific gene sets with 95 transcriptome data sets from human patients with chronic thromboembolic pulmonary hypertension led to the identification of more than 50 genes whose expression levels strongly correlated with the severity of right heart disease. Together, these data define a conserved, differentially regulated genetic network that coordinates progressive right heart failure in rats and humans.

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“…Regarding non-fibrillar collagens, the type VIII subunit (included in the subfamily of network-forming collagens) participates in cardiogenesis, while reduced expression is reported in physiological adult myocardium. In cardiovascular diseases, type VIII collagen has been implicated in cardiac dilatation-derived heart failure following pressure overload [ 24 ], carotid artery distensibility [ 25 ], and atrial fibrillation [ 26 ]. In fact, fibroblasts isolated from col8-knock-out mice displayed lower expression of transforming growth factor-β and α-smooth muscle actin, key players in post-MI cardiac fibrosis [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Fibrillar and Non-Fibrillar Collagens Involved in Fibrotic Scar Formation after Myocardial Infarction

Ortega,

Fábrega-García,

Molina-García

et al. 2024

IJMS

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Following myocardial infarction (MI), adverse remodeling depends on the proper formation of fibrotic scars, composed of type I and III collagen. Our objective was to pinpoint the participation of previously unreported collagens in post-infarction cardiac fibrosis. Gene (qRT-PCR) and protein (immunohistochemistry followed by morphometric analysis) expression of fibrillar (types II and XI) and non-fibrillar (types VIII and XII) collagens were determined in RNA-sequencing data from 92 mice undergoing myocardial ischemia; mice submitted to permanent (non-reperfused MI, n = 8) or transient (reperfused MI, n = 8) coronary occlusion; and eight autopsies from chronic MI patients. In the RNA-sequencing analysis of mice undergoing myocardial ischemia, increased transcriptomic expression of collagen types II, VIII, XI, and XII was reported within the first week, a tendency that persisted 21 days afterwards. In reperfused and non-reperfused experimental MI models, their gene expression was heightened 21 days post-MI induction and positively correlated with infarct size. In chronic MI patients, immunohistochemistry analysis demonstrated their presence in fibrotic scars. Functional analysis indicated that these subunits probably confer tensile strength and ensure the cohesion of interstitial components. Our data reveal that novel collagens are present in the infarcted myocardium. These data could lay the groundwork for unraveling post-MI fibrotic scar composition, which could ultimately influence patient survivorship.

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Deletion of type VIII collagen reduces blood pressure, increases carotid artery functional distensibility and promotes elastin deposition

Abstract: Highlights The matrix protein collagen VIII influences conduit artery compliance. Collagen VIII negatively regulates elastin. Collagen VIII KO increases elastin synthesis and content in carotid arteries. Collagen VIII and elastin exert opposing regulation of smooth muscle cell phenotypes.

Cited by 11 publications

References 55 publications

Read-depth based approach on whole genome resequencing data reveals important insights into the copy number variation (CNV) map of major global buffalo breeds

Read-depth based approach on whole genome resequencing data reveals important insights into the copy number variation (CNV) map of major global buffalo breeds

A common gene signature of the right ventricle in failing rat and human hearts

Novel Fibrillar and Non-Fibrillar Collagens Involved in Fibrotic Scar Formation after Myocardial Infarction

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