Purinergic Regulation of Endothelial Barrier Function

Aslam, Muhammad; Gündüz, Dursun; Troidl, Christian; Heger, Jacqueline; Hamm, Christian W.; Schulz, Rainer

doi:10.3390/ijms22031207

Cited by 25 publications

(19 citation statements)

References 151 publications

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“…Release of adipocyte-derived proinflammatory cytokines and adipokines into the bloodstream creates a systemic state of chronic, low-grade inflammation. This systemic inflammation can cause microvascular dysfunction and increase vascular permeability, enabling substances produced by obese adipose tissue to gain entrance into vital organs and tissues, thus leading to cardiovascular and metabolic complications (20)(21)(22).…”

Section: Adipocyte Location Expansion and Remodeling In Obesitymentioning

confidence: 99%

Obesity and its effects on the esophageal mucosal barrier

Paris

Ekeanyanwu

Jiang

et al. 2021

American Journal of Physiology-Gastrointestinal and Liver Physi

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Obesity is associated with gastroesophageal reflux disease (GERD) and its complications including reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Traditionally, these associations have been attributed to the mechanical effect of abdominal fat in increasing intra-abdominal pressure, thereby promoting gastroesophageal reflux and causing disruption of anti-reflux mechanisms at the esophagogastric junction. However, recent studies suggest that visceral adipose tissue (VAT) produces numerous cytokines that can cause esophageal inflammation and impair esophageal mucosal barrier integrity through reflux-independent mechanisms that render the esophageal mucosa especially susceptible to GERD-induced injury. In this report, we review mechanisms of esophageal mucosal defense, the genesis and remodeling of visceral adipose tissue during obesity, and the potential role of substances produced by VAT, especially the VAT that encircles the esophagogastric junction, in the impairment of esophageal mucosal barrier integrity that leads to the development of GERD complications.

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Section: Adipocyte Location Expansion and Remodeling In Obesitymentioning

confidence: 99%

Obesity and its effects on the esophageal mucosal barrier

Paris

Ekeanyanwu

Jiang

et al. 2021

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…These observations along with a profound inhibitory effect of butyrate on VEGFα production suggest that VEGF may play a key role in the increased vascular permeability in hypoxic animals. In addition, the contribution of other cytokines and extracellular nucleotides, such as ATP, to pulmonary vascular permeability is very likely, as ATP and other nucleotides can be increased in the extracellular space under hypoxic conditions [ 64 , 65 , 66 ]. The barrier-protective effect of butyrate observed in the lungs was reproduced in vitro on RMVEC.…”

Section: Discussionmentioning

confidence: 99%

The Short-Chain Fatty Acid Butyrate Attenuates Pulmonary Vascular Remodeling and Inflammation in Hypoxia-Induced Pulmonary Hypertension

Karoor

Strassheim

Sullivan

et al. 2021

IJMS

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Pulmonary hypertension (PH) is a progressive cardiovascular disorder in which local vascular inflammation leads to increased pulmonary vascular remodeling and ultimately to right heart failure. The HDAC inhibitor butyrate, a product of microbial fermentation, is protective in inflammatory intestinal diseases, but little is known regarding its effect on extraintestinal diseases, such as PH. In this study, we tested the hypothesis that butyrate is protective in a Sprague–Dawley (SD) rat model of hypoxic PH. Treatment with butyrate (220 mg/kg intake) prevented hypoxia-induced right ventricular hypertrophy (RVH), hypoxia-induced increases in right ventricular systolic pressure (RVSP), pulmonary vascular remodeling, and permeability. A reversal effect of butyrate (2200 mg/kg intake) was observed on elevated RVH. Butyrate treatment also increased the acetylation of histone H3, 25–34 kDa, and 34–50 kDa proteins in the total lung lysates of butyrate-treated animals. In addition, butyrate decreased hypoxia-induced accumulation of alveolar (mostly CD68+) and interstitial (CD68+ and CD163+) lung macrophages. Analysis of cytokine profiles in lung tissue lysates showed a hypoxia-induced upregulation of TIMP-1, CINC-1, and Fractalkine and downregulation of soluble ICAM (sICAM). The expression of Fractalkine and VEGFα, but not CINC-1, TIMP-1, and sICAM was downregulated by butyrate. In rat microvascular endothelial cells (RMVEC), butyrate (1 mM, 2 and 24 h) exhibited a protective effect against TNFα- and LPS-induced barrier disruption. Butyrate (1 mM, 24 h) also upregulated tight junctional proteins (occludin, cingulin, claudin-1) and increased the acetylation of histone H3 but not α-tubulin. These findings provide evidence of the protective effect of butyrate on hypoxic PH and suggest its potential use as a complementary treatment for PH and other cardiovascular diseases.

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“…GJ channels could contribute to the hyperpermeability mechanism because of their proximity and interactions with other junction proteins [170][171][172][173]. GJ channels and a hemichannel opening could be involved in hyperpermeability because the development of hyperpermeability is associated with an agonist-induced increment in the endothelial intracellular calcium concentration ([Ca 2+ ] i ), and maintaining hyperpermeability over time depends on an extracellular Ca 2+ influx [174][175][176][177][178][179][180], while ATP signaling is related to hyperpermeability mainly through purinergic receptor activation [181,182].…”

Section: Connexin Proteins In Postcapillary Venules Hyperpermeabilitymentioning

confidence: 99%

Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function

Burboa

Puebla

Gaete

et al. 2022

IJMS

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Microcirculation homeostasis depends on several channels permeable to ions and/or small molecules that facilitate the regulation of the vasomotor tone, hyperpermeability, the blood–brain barrier, and the neurovascular coupling function. Connexin (Cxs) and Pannexin (Panxs) large-pore channel proteins are implicated in several aspects of vascular physiology. The permeation of ions (i.e., Ca2+) and key metabolites (ATP, prostaglandins, D-serine, etc.) through Cxs (i.e., gap junction channels or hemichannels) and Panxs proteins plays a vital role in intercellular communication and maintaining vascular homeostasis. Therefore, dysregulation or genetic pathologies associated with these channels promote deleterious tissue consequences. This review provides an overview of current knowledge concerning the physiological role of these large-pore molecule channels in microcirculation (arterioles, capillaries, venules) and in the neurovascular coupling function.

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Purinergic Regulation of Endothelial Barrier Function

Cited by 25 publications

References 151 publications

Obesity and its effects on the esophageal mucosal barrier

Obesity and its effects on the esophageal mucosal barrier

The Short-Chain Fatty Acid Butyrate Attenuates Pulmonary Vascular Remodeling and Inflammation in Hypoxia-Induced Pulmonary Hypertension

Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function

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