Apelin modulates pathological remodeling of lymphatic endothelium after myocardial infarction

Tatin, Florence; Renaud-Gabardos, Edith; Godet, Anne-Claire; Hantelys, Fransky; Pujol, Françoise; Morfoisse, Florent; Calise, Denis; Viars, Fanny; Valet, Philippe; Masri, Bernard; Prats, Anne-Catherine; Garmy‐Susini, Barbara

doi:10.1172/jci.insight.93887

Cited by 73 publications

(97 citation statements)

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“…Recently published studies revealed the importance of the cardiac lymphatic vasculature and its remodelling during the recovery phase after myocardial infarction (MI) (Ishikawa et al , ; Klotz et al , ; Henri et al , ; Tatin et al , ). Notably, the importance of ILK in cardiomyocytes and in regulating cardiac function was previously reported by several publications (Bendig et al , ; Lu et al , ; White et al , ; Ding et al , ; Gu et al , ; Traister et al , ).…”

Section: Resultsmentioning

confidence: 99%

“…Lymphatic network formation requires a careful balance of pro‐ and anti‐lymphangiogenic regulators (reviewed by Schulte‐Merker et al , ; Klein & Caron, ; Sabine et al , ). Disturbing this balance leads to hypo‐ or hyperplasia of lymphatic vessels, which is of clinical importance across multiple pathologies (Rutkowski et al , ; Klotz et al , ; Gousopoulos et al , , ; Henri et al , ; Tatin et al , ). Here, we identified ILK to be required to limit VEGFR3 signalling and lymphatic vascular growth in developmental, physiological and pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…The importance of the lymphatic vasculature is demonstrated by its numerous physiological functions, including maintenance of fluid homeostasis, facilitation of immune response and uptake of lipids and vitamins. Moreover, it is involved in pathological conditions such as primary and secondary lymphoedema, obesity development, tumour cell dissemination and growth, reverse cholesterol transport, hypertension, glaucoma, inflammation and regeneration or damage after myocardial infarction (Karkkainen et al , ; Skobe et al , ; Harvey et al , ; Wilting et al , ; Martel et al , ; Thomson et al , ; Huang et al , ; Klotz et al , ; Escobedo et al , ; Gousopoulos et al , ; Lund et al , ; Tatin et al , ; Zhang et al , ). Growth of lymphatic vessels, known as lymphangiogenesis, is critically regulated by vascular endothelial growth factor receptor‐3 (VEGFR3) signalling, also required for normal blood vascular development (Dumont et al , ; Veikkola et al , ).…”

Section: Introductionmentioning

confidence: 99%

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Identification of ILK as a critical regulator of VEGFR 3 signalling and lymphatic vascular growth

et al. 2018

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Vascular endothelial growth factor receptor‐3 (VEGFR3) signalling promotes lymphangiogenesis. While there are many reported mechanisms of VEGFR3 activation, there is little understanding of how VEGFR3 signalling is attenuated to prevent lymphatic vascular overgrowth and ensure proper lymph vessel development. Here, we show that endothelial cell‐specific depletion of integrin‐linked kinase (ILK) in mouse embryos hyper‐activates VEGFR3 signalling and leads to overgrowth of the jugular lymph sacs/primordial thoracic ducts, oedema and embryonic lethality. Lymphatic endothelial cell (LEC)‐specific deletion of Ilk in adult mice initiates lymphatic vascular expansion in different organs, including cornea, skin and myocardium. Knockdown of ILK in human LECs triggers VEGFR3 tyrosine phosphorylation and proliferation. ILK is further found to impede interactions between VEGFR3 and β1 integrin in vitro and in vivo, and endothelial cell‐specific deletion of an Itgb1 allele rescues the excessive lymphatic vascular growth observed upon ILK depletion. Finally, mechanical stimulation disrupts the assembly of ILK and β1 integrin, releasing the integrin to enable its interaction with VEGFR3. Our data suggest that ILK facilitates mechanically regulated VEGFR3 signalling via controlling its interaction with β1 integrin and thus ensures proper development of lymphatic vessels.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of ILK as a critical regulator of VEGFR 3 signalling and lymphatic vascular growth

et al. 2018

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“…Experimental myocardial infarction of the mouse heart stimulates both angiogenesis lymphangiogenesis, further suggesting an important role of lymphatics in overall tissue homeostasis in the heart (543). The peptide apelin appears to have an important role in regulating lymphangiogenesis under these circumstances (1052). In humans, an increase in new lymphatic vessel formation was reported near the edges of necrotic tissue following myocardial infarction, in scars, and in areas of reactive pericarditis (534).…”

Section: Organization and Anatomy Of The Lymphatic Systemmentioning

confidence: 99%

Lymphatic Vessel Network Structure and Physiology

Breslin

Yang

Scallan

et al. 2018

Comprehensive Physiology

243

258

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The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease.

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“…In the in vivo and in vitro model of myocardial infarction, some groups have confirmed that both apelin and Elabela reduced infarct size by phosphorylating PI3K/Akt and ERK1/2 signal pathways (Perjés et al, 2016;Zeng et al, 2009). Furthermore, Azizi et al and other scientists have shown that NO may limit the infarct size as a protective medium, and its expression can be increased by apelin-induced (Azizi, Faghihi, Imani, Roghani, & Nazari, 2013;Rastaldo et al, 2011 , maintains cell-ligation integrity by regulating S1P secretion in lymphatic ECs (Tatin et al, 2017), as well as blocks mitochondrial division-mediated cell death by inhibiting p-Drp1Ser616 (Xu et al, 2017). Therefore, all these results indicate that apelin is expected to be a marker and therapeutic target for myocardial infarction.…”

Section: Myocardial Infarctionmentioning

confidence: 80%

Apelin/APJ system: A potential therapeutic target for endothelial dysfunction‐related diseases

Cheng

Luo

Huang

et al. 2018

Journal Cellular Physiology

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APJ is a G protein‐coupled receptor and its endogenous ligand is apelin. Studies have shown that apelin/APJ system is widely distributed in the body, especially highly expressed in the vascular endothelial cells (ECs). Numerous reports have demonstrated that apelin/APJ system plays an important role in the regulation of ECs function. Our lab has demonstrated that apelin‐13 is able to promote adhesion of monocyte‐human umbilical vein EC via 14‐3‐3, and reactive oxygen species‐autophagy signaling pathways. In this review, we concentrate on the regulatory mechanism of apelin/APJ system in EC, including promotion of proliferation, migration, and angiogenesis. Moreover, we also analyze the role of apelin/APJ on endothelial dysfunction‐related diseases including atherosclerosis, diabetes, hypertension, and myocardial infarction. Finally, we summarize the most commonly used agonists and antagonists of APJ. Therefore, apelin/APJ system is expected to be a therapeutic target for the treatment of endothelial dysfunction‐related diseases.

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Apelin modulates pathological remodeling of lymphatic endothelium after myocardial infarction

Cited by 73 publications

References 50 publications

Identification of ILK as a critical regulator of VEGFR 3 signalling and lymphatic vascular growth

Identification of ILK as a critical regulator of VEGFR 3 signalling and lymphatic vascular growth

Lymphatic Vessel Network Structure and Physiology

Apelin/APJ system: A potential therapeutic target for endothelial dysfunction‐related diseases

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