The role of lymphatic vessels in the heart

Cui, Yingjie

doi:10.1016/j.pathophys.2009.07.006

Cited by 42 publications

(40 citation statements)

References 42 publications

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“…4 Accordingly, surgical obstruction of cardiac lymphatics rapidly leads to myocardial edema with well-described acute, and chronic, as well, deleterious effects on cardiac function. [5][6][7] Clinically detectable myocardial edema is a frequent finding in the acute phase of myocardial ischemia, 8 initially because of vascular hyperpermeability. [9][10][11] Concurrently, there is rapid infiltration of neutrophils, macrophages, and other immune cells, which participate in the inflammatory tissue response to injury.…”

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confidence: 99%

Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

et al. 2016

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Background-The lymphatic system regulates interstitial tissue fluid balance, and lymphatic malfunction causes edema.The heart has an extensive lymphatic network displaying a dynamic range of lymph flow in physiology. Myocardial edema occurs in many cardiovascular diseases, eg, myocardial infarction (MI) and chronic heart failure, suggesting that cardiac lymphatic transport may be insufficient in pathology. Here, we investigate in rats the impact of MI and subsequent chronic heart failure on the cardiac lymphatic network. Further, we evaluate for the first time the functional effects of selective therapeutic stimulation of cardiac lymphangiogenesis post-MI. Methods and Results-We investigated cardiac lymphatic structure and function in rats with MI induced by either temporary occlusion (n=160) or permanent ligation (n=100) of the left coronary artery. Although MI induced robust, intramyocardial capillary lymphangiogenesis, adverse remodeling of epicardial precollector and collector lymphatics occurred, leading to reduced cardiac lymphatic transport capacity. Consequently, myocardial edema persisted for several months post-MI, extending from the infarct to noninfarcted myocardium. Intramyocardial-targeted delivery of the vascular endothelial growth factor receptor 3-selective designer protein VEGF-C C152S , using albumin-alginate microparticles, accelerated cardiac lymphangiogenesis in a dose-dependent manner and limited precollector remodeling post-MI. As a result, myocardial fluid balance was improved, and cardiac inflammation, fibrosis, and dysfunction were attenuated. Conclusions-We show that, despite the endogenous cardiac lymphangiogenic response post-MI, the remodeling and dysfunction of collecting ducts contribute to the development of chronic myocardial edema and inflammationaggravating cardiac fibrosis and dysfunction. Moreover, our data reveal that therapeutic lymphangiogenesis may be a promising new approach for the treatment of cardiovascular diseases. deleterious effects, including induction of blood vascular rarefaction and dysfunction and stimulation of cardiac fibrosis, contributing to the development of chronic heart failure . 14 Furthermore, many inflammatory mediators, and oxygen radicals generated during inflammation, as well, negatively affect lymphatic function, causing impairment of lymph flow and initiation of lymph edema and chronic inflammation. 15,16 It is noteworthy that clinically detectable myocardial edema, extending beyond the infarct zone, may persist for up to 6 to 12 months post-myocardial infarction (MI) in humans, which is suggestive of lymphatic insufficiency. 17,18Whether cardiac lymphatic dysfunction occurs after myocardial injury, and the impact this may have on myocardial fluid balance and cardiac inflammation, remains to be investigated. Moreover, although the advent of molecular lymphatic markers has fueled investigations into lymphatic anatomy, function, and growth in many organs, 19-21 only a handful of articles have assessed lymphangiogenesis in the heart. It was rec...

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Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

et al. 2016

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“…Angiogenesis advances delivery of both oxygen and energy substrates in peri-infarct and infarct area, and has the potential to salvage ischemic myocardium at early stages after MI [63]. Lymphangiogenesis in the peri-infarct area improves cardiac lymph flow leading to reduced lymphedema, thereby reducing a trigger for the development of interstitial fibrosis [64-66]. Davis et al [67] demonstrated in a rat model that chronic myocardial edema was accompanied by increased mRNA levels of Col I and III followed by significant increases in LV collagen deposition.…”

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confidence: 99%

Cardiomyocyte-specific Estrogen Receptor Alpha Increases Angiogenesis,Lymphangiogenesis and Reduces Fibrosis in the Female Mouse Heart Post-Myocardial Infarction

et al. 2014

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Experimental studies showed that 17β-estradiol (E2) and activated Estrogen Receptors (ER) protect the heart from ischemic injury. However, the underlying molecular mechanisms are not well understood. To investigate the role of ER-alpha (ERα) in cardiomyocytes in the setting of myocardial ischemia, we generated transgenic mice with cardiomyocyte-specific overexpression of ERα (ERα-OE) and subjected them to Myocardial Infarction (MI). At the basal level, female and male ERα-OE mice showed increased Left Ventricular (LV) mass, LV volume and cardiomyocyte length. Two weeks after MI, LV volume was significantly increased and LV wall thickness decreased in female and male WT-mice and male ERα-OE, but not in female ERα-OE mice. ERα-OE enhanced expression of angiogenesis and lymphangiogenesis markers (Vegf, Lyve-1), and neovascularization in the peri-infarct area in both sexes. However, attenuated level of fibrosis and higher phosphorylation of JNK signaling pathway could be detected only in female ERα-OE after MI. In conclusion, our study indicates that ERα protects female mouse cardiomyocytes from the sequelae of ischemia through induction of neovascularization in a paracrine fashion and impaired fibrosis, which together may contribute to the attenuation of cardiac remodelling.

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“…126,127 It has long been assumed that cardiac lymph flow depends only on external systolic compressive forces. Diastolic lymph flow might involve active lymphatic contraction, as cardiac lymph flow is maintained during conditions where cardiac contractility is impaired.…”

Section: -125mentioning

confidence: 99%

“…126,128,[130][131][132] It is also possible that impaired cardiac lymph flow can participate in several forms of cardiac pathology, such as dilated cardiomyopathy (DCM) and heart failure. 127,133,134 Inflammatory myocarditis provokes myocardial edema, and formation of inflammatory infiltrates of lymphocytes and macrophages; both can drive underlying lymphatic pumping disturbances. 135,136 Myocardial edema, in several forms of acute cardiac inflammation, is associated with increased myocardial lymph flow rate and decreased lymphatic outflow resistance.…”

Section: -125mentioning

confidence: 99%

Anatomy and roles of lymphatics in inflammatory diseases

Al‐Kofahi

Yun

Minagar

et al. 2017

Clinical & Exp Neuroim

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The lymphatic system maintains tissue homeostasis by transporting interstitial fluid, lipids and debris from tissues to the main circulation, and delivers antigen and antigen presenting cells to local lymph nodes where they elicit immune responses. During inflammation, lymph flow increases to limit edema and prevents tissue antigen-presenting cell transport. Lymphatics also adjust their contractile activity to increase fluid transfer during acute inflammation. Conversely, chronic inflammation can provoke lymphostasis, which might limit pathogen spread within the circulation; however, decreased lymph flow leads to the persistence of immune cells and mediators in tissues to intensifying injury. Here, we review lymphatic structure function within the gut, heart and central nervous system, discussing potential roles of these lymphatics in the etiology of inflammatory bowel disease, myocarditis and neurovascular disease, and as novel targets for therapeutic management of several disease states.

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The role of lymphatic vessels in the heart

Cited by 42 publications

References 42 publications

Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

Cardiomyocyte-specific Estrogen Receptor Alpha Increases Angiogenesis,Lymphangiogenesis and Reduces Fibrosis in the Female Mouse Heart Post-Myocardial Infarction

Anatomy and roles of lymphatics in inflammatory diseases

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