Serotonin and Pulmonary Hypertension;
            <i>Sex and Drugs and ROCK and Rho</i>

MacLean, Margaret R.; Fanburg, Barry L.; Hill, Nicolas; Lazarus, Howard M.; Pack, Thomas F.; Palacios, Michelle; Penumatsa, Krishna; Wring, Stephen A.

doi:10.1002/cphy.c220004

Cited by 15 publications

(10 citation statements)

References 162 publications

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“…In addition, our study focused on local neural restoration of DW; however, restoration of peripheral neural function may deliver signal transduction to the brain center and exert emotional mediation. Considering the evidence that supports the beneficial role of positive mood in promoting cell proliferation and differentiation, [ 35 ] further studies exploring the crosstalk between the peripheral and central nervous systems during the wound healing process may be useful in developing more systematic repair strategies.…”

Section: Discussionmentioning

confidence: 99%

A Whole‐Course‐Repair System Based on Neurogenesis‐Angiogenesis Crosstalk and Macrophage Reprogramming Promotes Diabetic Wound Healing

et al. 2023

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Diabetic wound (DW) therapy is currently a big challenge in medicine and strategies to enhance neurogenesis and angiogenesis have appeared to be a promising direction. However, the current treatments have failed to coordinate neurogenesis and angiogenesis simultaneously, leading to an increased disability rate caused by DWs. Herein, a whole‐course‐repair system is introduced by a hydrogel to concurrently achieve a mutually supportive cycle of neurogenesis‐angiogenesis under a favorable immune‐microenvironment. This hydrogel can first be one‐step packaged in a syringe for later in situ local injections to cover wounds long‐termly for accelerated wound healing via the synergistic effect of magnesium ions (Mg2+) and engineered small extracellular vesicles (sEVs). The self‐healing and bio‐adhesive properties of the hydrogel make it an ideal physical barrier for DWs. At the inflammation stage, the formulation can recruit bone marrow‐derived mesenchymal stem cells to the wound sites and stimulate them toward neurogenic differentiation, while providing a favorable immune microenvironment via macrophage reprogramming. At the proliferation stage of wound repair, robust angiogenesis occurs by the synergistic effect of the newly differentiated neural cells and the released Mg2+, allowing a regenerative neurogenesis‐angiogenesis cycle to take place at the wound site. This whole‐course‐repair system provides a novel platform for combined DW therapy.

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Section: Discussionmentioning

confidence: 99%

A Whole‐Course‐Repair System Based on Neurogenesis‐Angiogenesis Crosstalk and Macrophage Reprogramming Promotes Diabetic Wound Healing

et al. 2023

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“…Primary pulmonary hypertension is associated with a substantial increase in 5-HT 2B R expression in pulmonary arteries [ 55 ]. At the same time, in pulmonary hypertension, the synthesis of 5-HT in EC increases [ 5 ], which can cause activation of intracellular 5HT 1B R. As a result, 5-HT, as we assume, may induce a sharp increase in [Ca 2+ ] i in the EC, leading to their damage. The risk of pulmonary hypertension in humans is increased under the action of dexfenfluramine, which is an active metabolite and an agonist of 5-HT 2B R. Bloodworth et al [ 56 ] demonstrated that bone marrow-derived proangiogenic cells contribute to experimental pulmonary hypertension in a 5-HT 2B R signaling-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…In the brain, 5-HT is synthesized in neurons in raphe nuclei of the brain stem [ 4 ]. The 5-HT is also produced in the pulmonary endothelial [ 5 ] and neuroendocrine [ 6 ] cells, skin Merkel cells [ 7 ], and taste buds [ 8 ]. The action of 5-HT is mediated by seven types of 5-HT receptors (5-HTR), six of which are G-protein-coupled receptors (5-HT 1,2,4,5,6,7 R), and one type (5-HT 3 R) is a cationic channel [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Interaction of 5-HT1B and 5-HT2B Receptors in Cytoplasmic Ca2+ Regulation in Human Umbilical Vein Endothelial Cells: Possible Involvement in Pathologies

Rybakova,

Avdonin,

Trufanov

et al. 2023

IJMS

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The aim of this work was to explore the involvement of 5-HT1B and 5-HT2B receptors (5-HT1BR and 5-HT2BR) in the regulation of free cytoplasmic calcium concentration ([Ca2+]i) in human umbilical vein endothelial cells (HUVEC). We have shown by quantitative PCR analysis, that 5-HT1BR and 5-HT2BR mRNAs levels are almost equal in HUVEC. Immunofluorescent staining demonstrated, that 5-HT1BR and 5-HT2BR are expressed both in plasma membrane and inside the cells. Intracellular 5-HT1BR are localized mainly in the nuclear region, whereas 5-HT2BR receptors are almost evenly distributed in HUVEC. 5-HT, 5-HT1BR agonist CGS12066B, or 5-HT2BR agonist BW723C86 added to HUVEC caused a slight increase in [Ca2+]i, which was much lower than that of histamine, ATP, or SFLLRN, an agonist of protease-activated receptors (PAR1). However, activation of 5-HT1BR with CGS12066B followed by activation of 5-HT2BR with BW723C86 manifested a synergism of response, since several-fold higher rise in [Ca2+]i occurred. CGS12066B caused more than a 5-fold increase in [Ca2+]i rise in HUVEC in response to 5-HT. This 5-HT induced [Ca2+]i rise was abolished by 5-HT2BR antagonist RS127445, indicating that extracellular 5-HT acts through 5-HT2BR. Synergistic [Ca2+]i rise in response to activation of 5-HT1BR and 5-HT2BR persisted in a calcium-free medium. It was suppressed by the phospholipase C inhibitor U73122 and was not inhibited by the ryanodine and NAADP receptors antagonists dantrolene and NED-19. [Ca2+]i measurements in single cells demonstrated that activation of 5-HT2BR alone by BW723C86 caused single asynchronous [Ca2+]i oscillations in 19.8 ± 4.2% (n = 3) of HUVEC that occur with a long delay (66.1 ± 4.3 s, n = 71). On the contrary, histamine causes a simultaneous and almost immediate increase in [Ca2+]i in all the cells. Pre-activation of 5-HT1BR by CGS12066B led to a 3–4 fold increase in the number of HUVEC responding to BW723C86, to synchronization of their responses with a delay shortening, and to the bursts of [Ca2+]i oscillations in addition to single oscillations. In conclusion, to get a full rise of [Ca2+]i in HUVEC in response to 5-HT, simultaneous activation of 5-HT1BR and 5-HT2BR is required. 5-HT causes an increase in [Ca2+]i via 5-HT2BR while 5-HT1BR could be activated by the membrane-permeable agonist CGS12066B. We hypothesized that CGS12066B acts via intracellular 5-HT1BR inaccessible to extracellular 5-HT. Intracellular 5-HT1BR might be activated by 5-HT which could be accumulated in EC under certain pathological conditions.

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“…Alterations of PASMCs communicate with PAECs and play a major regulatory role in the pathological development of PH [ 90 ]. PAECs in PH lose the ability to modulate the appropriate moderate balance between vasoconstrictors, such as endothelin-1 (ET-1) and serotonin, and vasodilators, such as nitric oxide (NO) and prostacyclin [ 91 , 92 , 93 , 94 ]. The capacity of PAECs is to maintain a regular vascular network by secreting vasoactive factors, which affects the interactions between PAECs and PASMCs, and regulates multicellular contraction, proliferation, and survival.…”

Section: Media Remodeling In Pulmonary Vascular Remodelingmentioning

confidence: 99%

Pulmonary Vascular Remodeling in Pulmonary Hypertension

Jia

Wang

Yan

et al. 2023

JPM

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Pulmonary vascular remodeling is the critical structural alteration and pathological feature in pulmonary hypertension (PH) and involves changes in the intima, media and adventitia. Pulmonary vascular remodeling consists of the proliferation and phenotypic transformation of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) of the middle membranous pulmonary artery, as well as complex interactions involving external layer pulmonary artery fibroblasts (PAFs) and extracellular matrix (ECM). Inflammatory mechanisms, apoptosis and other factors in the vascular wall are influenced by different mechanisms that likely act in concert to drive disease progression. This article reviews these pathological changes and highlights some pathogenetic mechanisms involved in the remodeling process.

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Serotonin and Pulmonary Hypertension; Sex and Drugs and ROCK and Rho

Cited by 15 publications

References 162 publications

A Whole‐Course‐Repair System Based on Neurogenesis‐Angiogenesis Crosstalk and Macrophage Reprogramming Promotes Diabetic Wound Healing

A Whole‐Course‐Repair System Based on Neurogenesis‐Angiogenesis Crosstalk and Macrophage Reprogramming Promotes Diabetic Wound Healing

Synergistic Interaction of 5-HT1B and 5-HT2B Receptors in Cytoplasmic Ca2+ Regulation in Human Umbilical Vein Endothelial Cells: Possible Involvement in Pathologies

Pulmonary Vascular Remodeling in Pulmonary Hypertension

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