Semaphorins in cardiovascular medicine

Corà, Davide; Astanina, Elena; Giraudo, Enrico; Bussolino, Federico

doi:10.1016/j.molmed.2014.07.005

Cited by 17 publications

(10 citation statements)

References 84 publications

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“…To adapt to a hypoxic environment, TP increased expression of the VEGFA gene in vivo and changed their cardiovascular response to hypoxia. The increased VEGFA expression might increase blood flow and enhance cardiac pumping [ 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

Gene expression of vascular endothelial growth factor A and hypoxic adaptation in Tibetan pig

Zhang

Qiangba

Shang

et al. 2016

J Animal Sci Biotechnol

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Background: Vascular endothelial growth factor A (VEGFA) can induce endothelial cell proliferation, promote cell migration, and inhibit apoptosis. These processes play key roles in physiological blood vessel formation and pathological angiogenesis. Methods: In this study, we examined VEGFA gene expression in the heart, liver, and kidney of Tibetan pigs (TP), Yorkshire pigs that migrated to high altitudes (YH), and Yorkshire pigs that lived at low altitudes (YL). We used PCR and Sanger sequencing to screen for single nucleotide polymorphisms (SNPs) in 5ʹ-flanking DNA and exons of the VEGFA gene. Quantitative real-time PCR and western blots were used to measure expression levels and PCR products were sequenced. Results: Results showed that the VEGFA mRNA and protein expression in heart, liver and kidney of TP was higher than that in YH and YL. In addition, the mRNA sequence of the pig VEGFA gene was conserved among pig breeds, and only five SNPs were found in the 5ʹ-flanking region of the VEGFA gene, the allele frequency distributions of the 5 SNPs were not significantly different between the TP, Yorkshire (YL), and Diannan small-ear (DN) pig populations. Conclusion: In conclusion, the Tibetan pig showed high levels of VEGFA gene expression in several hypoxic tissues, which suggests that the VEGFA gene may play a major functional role in hypoxic adaptation.

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Section: Discussionmentioning

confidence: 99%

Gene expression of vascular endothelial growth factor A and hypoxic adaptation in Tibetan pig

Zhang

Qiangba

Shang

et al. 2016

J Animal Sci Biotechnol

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“…In particular, members of the Class III SEMA family have been reported to affect endothelial biology [5][6][7]. Class III SEMAs are secreted proteins typically composed of a signal peptide for cellular secretion, a SEMA domain (involved in dimerization and receptor binding to plexins/neuropilins), an Immunoglobulin (Ig) domain, a PSI domain (domain found in Plexins, Semaphorins and Integrins necessary for receptor binding to neuropilins) and a basic tail [8].…”

Section: Introductionmentioning

confidence: 99%

Endothelial Semaphorin 3F Maintains Endothelial Barrier Function and Inhibits Monocyte Migration

Zhang

Vreeken

Junaid

et al. 2020

IJMS

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In normal physiology, endothelial cells (ECs) form a vital barrier between the blood and underlying tissue controlling leukocyte diapedesis and vascular inflammation. Emerging data suggest that neuronal guidance cues, typically expressed during development, have roles outside the nervous system in vascular biology and immune responses. In particular, Class III semaphorins have been reported to affect EC migration and angiogenesis. While ECs express high levels of semaphorin 3F (SEMA3F), little is known about its function in mature ECs. Here we show that SEMA3F expression is reduced by inflammatory stimuli and increased by laminar flow. Endothelial cells exposed to laminar flow secrete SEMA3F, which subsequently binds to heparan sulfates on the surface of ECs. However, under pro-inflammatory conditions, reduced levels of SEMA3F make ECs more prone to monocyte diapedesis and display impaired barrier function as measured with an electric cell–substrate impedance sensing system and a microfluidic system. In addition, we demonstrate that SEMA3F can directly inhibit the migration of activated monocytes. Taken together, our data suggest an important homeostatic function for EC-expressed SEMA3F, serving as a mediator of endothelial quiescence.

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“…Semaphorin3A (Sema3A) is a secreted glycoprotein first identified as a chemo-repellent during axonal guidance [26], and crucial for embryonic development [3, 10]. In addition to its involvement in cell motility [12] and neuronal-vascular growth [15, 37], Sema3A has also been ascribed with tumor-reducing capacities [8] and anti-inflammatory properties during dermatitis [31], autoimmune arthritis [6] and kidney injury [33].…”

Section: Introductionmentioning

confidence: 99%

Sema3A promotes the resolution of cardiac inflammation after myocardial infarction

et al. 2017

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Optimal healing after myocardial infarction requires not only the induction of inflammation, but also its timely resolution. In patients, 30 days post myocardial infarction, circulating monocytes have increased expression of Semaphorin3A (Sema3A) as compared to directly after admission. This increased expression coincides with increased expression of Cx3CR1—a marker of non-classical monocytes that are important for immune resolution hence proper wound healing. In mice, the expression of Sema3A also increases in response to myocardial ischemia being expressed by infiltrating leukocytes. Comparing Sema3A heterozygote (HZ) and wild type (WT) mice post myocardial infarction, revealed increased presence of leukocytes in the cardiac tissues of HZ mice as compared to WT, with no differences in capillary density, collagen deposition, cardiomyocyte surface area, chemokine—or adhesion molecules expression. Whilst infarct sizes were similar 14 days after myocardial infarction in both genotypes, Sema3A HZ mice had thinner infarcts and reduced cardiac function as compared to their WT littermates. In vitro experiments were conducted to study the role of Sema3A in inflammation and resolution of inflammation as a potential explanation for the differences in leukocyte recruitment and cardiac function observed in our in vivo experiments. Here, recombinant Sema3A protein was able to affect the pro-inflammatory state of cultured bone marrow derived macrophages. First, the pro-inflammatory state was altered by the induced apoptosis of classical macrophages in the presence of Sema3A. Second, Sema3A promoted the polarization of classical macrophages to resolution-phase macrophages and enhanced their efferocytotic ability, findings that were reflected in the infarcted cardiac tissue of the Sema3A HZ mice. Finally, we demonstrated that besides promoting resolution of inflammation, Sema3A was also able to retard the migration of monocytes to the myocardium. Collectively our data demonstrate that Sema3A reduces cardiac inflammation and improves cardiac function after myocardial infarction by promoting the resolution of inflammation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-017-0630-5) contains supplementary material, which is available to authorized users.

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Semaphorins in cardiovascular medicine

Cited by 17 publications

References 84 publications

Gene expression of vascular endothelial growth factor A and hypoxic adaptation in Tibetan pig

Gene expression of vascular endothelial growth factor A and hypoxic adaptation in Tibetan pig

Endothelial Semaphorin 3F Maintains Endothelial Barrier Function and Inhibits Monocyte Migration

Sema3A promotes the resolution of cardiac inflammation after myocardial infarction

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