Coronary Arteries Shake Up Developmental Dogma

Hu, Shing; Kurpios, Natasza A.

doi:10.1016/j.devcel.2018.11.044

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…Endothelial cells in the coronary vasculature are derived from the sinus venosus, endocardium, and proepicardium that populate complementary regions of the heart . A majority of coronary endothelial cells in the embryonic ventricular wall are thought to originate from the sinus venosus localized on the dorsal surface of the myocardium, and they migrate between the epicardium and myocardium around E11.5 . A dorsal view of the whole‐mount CD31‐stained ventricles shows the endothelial cell plexus organized within the ventricles more prominently and extended toward the apical region of the heart in normoxic hearts compared to hypoxic hearts (Figure 3A, normoxia vs hypoxia, white arrowheads).…”

Section: Resultsmentioning

confidence: 99%

Defective coronary vessel organization and reduction of VEGF‐A in mouse embryonic hearts with gestational mild hypoxia

Cai

Alkassis

Kasahara

2020

Developmental Dynamics

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Background: Vasculature is formed by responding to homeostatic tissue demands including in developing hearts. Hypoxia generally stimulates vascular formation in which vascular endothelial growth factor A (VEGF-A) plays a critical role. Gestational hypoxia increases the risk of low intrauterine growth and low birth weight, both of which are known to increase the risk of the fetus developing cardiovascular defects. In fact, continuous gestational mild hypoxia (14% O 2 ) from the mid-embryonic stage causes cardiac anomalies accompanied by a thinning compact layer in mice in vivo. Because coronary vasculature formation is necessary for compact layers to thicken, we hypothesized that defective coronary vessel organization is related to the thinning compact layer under gestational hypoxia conditions. Results: Continuous gestational mild hypoxia (14% O 2 ) applied from embryonic day 10.5 (E10.5) reduced the expression of VEGF-A mRNA and proteins by over 60% in E12.5 hearts relative to control normoxic hearts. Formation of CD31-positive vascular plexus, blood islands, and microvessels in embryonic ventricles were stunted by gestational hypoxia compared to control E12.5 hearts. Conclusions: Our results suggest that mild hypoxia (14% O 2 ) does not induce coronary vessel organization or VEGF-A expression in developing mouse hearts, opposing the general effects of hypoxia-triggering vascular organization and VEGF-A expression. K E Y W O R D Scoronary vessel, heart, hypoxia, VEGF-A

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Section: Resultsmentioning

confidence: 99%

Defective coronary vessel organization and reduction of VEGF‐A in mouse embryonic hearts with gestational mild hypoxia

Cai

Alkassis

Kasahara

2020

Developmental Dynamics

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“…Failure of coronary circulation may result in ischemic infarction and cardiac arrest, which is so far the leading cause of death worldwide. Therefore, an understanding of coronary vessel formation during embryonic development, their maintenance in adult hearts, and their remodeling under pathological conditions will be extremely important for developing new strategies to prevent or treat ischemic heart diseases (Hu and Kurpios, 2018;Lupu et al, 2020). Although the origin of coronary vessels during embryonic development is still under debate, recent studies using cell lineage tracing and single-cell transcriptome analysis provided convincing evidence that coronary vessels derive from endothelial sprouts of the sinus venosus with a small contribution from the endocardium lining the cardiac chambers (Red-Horse et al, 2010;Su et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Histone Lysine Methyltransferase SETD2 Regulates Coronary Vascular Development in Embryonic Mouse Hearts

Chen

Wang

et al. 2021

Front. Cell Dev. Biol.

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Congenital heart defects are the most common birth defect and have a clear genetic component, yet genomic structural variations or gene mutations account for only a third of the cases. Epigenomic dynamics during human heart organogenesis thus may play a critical role in regulating heart development. However, it is unclear how histone mark H3K36me3 acts on heart development. Here we report that histone-lysine N-methyltransferase SETD2, an H3K36me3 methyltransferase, is a crucial regulator of the mouse heart epigenome. Setd2 is highly expressed in embryonic stages and accounts for a predominate role of H3K36me3 in the heart. Loss of Setd2 in cardiac progenitors results in obvious coronary vascular defects and ventricular non-compaction, leading to fetus lethality in mid-gestation, without affecting peripheral blood vessel, yolk sac, and placenta formation. Furthermore, deletion of Setd2 dramatically decreased H3K36me3 level and impacted the transcriptional landscape of key cardiac-related genes, including Rspo3 and Flrt2. Taken together, our results strongly suggest that SETD2 plays a primary role in H3K36me3 and is critical for coronary vascular formation and heart development in mice.

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“…This process is regulated by Notch signaling [41] . Importantly, Red-Horse et al [42] and Pérez-Pomares et al [43] found that some mouse coronary artery SMCs originate from the sinus venosus; the venous endothelial cells travel to the heart muscle, where they form a vascular plexus, which is then remodeled into arteries, veins, and capillaries [42,44] . All these findings provide insights into the detailed development of coronary SMCs.…”

Section: A Lineage Perspective Of Vsmcs Developmentmentioning

confidence: 96%

Vascular Smooth Muscle Cell Development and Cardiovascular Malformations

Liu

Kong

2021

Cardiology Discovery

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Vascular smooth muscle cells (VSMCs) have diverse biological functions that include maintaining the vascular structure and recruiting progenitors to form the embryonic vascular system. Accumulating evidence suggests that the VSMCs are not just derived from the mesoderm, as previously thought, but have diverse developmental origins. Lineage tracing analysis indicates that VSMCs have at least 7 different origins, thereby giving it the characteristic of a mosaic tissue. The crucial role of the diverse origins of the VSMCs has been recognized in relation to blood vessel function and diseases such as arteriosclerosis. The VSMC distribution in cardiovascular development and whether and how their heterogeneous origins contribute to the overall cardiovascular development continue to be topics of research. Here, we review the current state of research, mainly focusing on the role of VSMCs in cardiovascular development. We emphasize the following biological pathways: (1) normal course of development of VSMCs and their diverse origins in relation to cardiovascular development, (2) signaling regulation of progenitor cell development and differentiation into VSMCs, and (3) abnormal development of vascular smooth muscle and the associated cardiovascular malformations.

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Coronary Arteries Shake Up Developmental Dogma

Cited by 4 publications

References 9 publications

Defective coronary vessel organization and reduction of VEGF‐A in mouse embryonic hearts with gestational mild hypoxia

Defective coronary vessel organization and reduction of VEGF‐A in mouse embryonic hearts with gestational mild hypoxia

Histone Lysine Methyltransferase SETD2 Regulates Coronary Vascular Development in Embryonic Mouse Hearts

Vascular Smooth Muscle Cell Development and Cardiovascular Malformations

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