• Title/Summary/Keyword: vascular channel

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Diagnostic and Therapeutic Implications of the Vascular Endothelial Growth Factor Family in Cancer

  • Riaz, Syeda Kiran;Iqbal, Yasmeen;Malik, Muhammad Faraz Arshad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1677-1682
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    • 2015
  • Cancer progression is attained by uncontrolled cell division and metastasis. Increase in tumor size triggers different vascular channel formation to address cell nutritional demands. These channels are responsible for transferring of nutrients and gaseous to the cancer cells. Cancer vascularization is regulated by numerous factors including vascular endothelial growth factors (VEGFs). These factors play an important role during embryonic development. Members included in this group are VEGFA, VEGFB, VEGFC, PIGF and VEGFD which markedly influence cellular growth and apoptosis. Being freely diffusible these proteins act in both autocrine and paracrine fashions. In this review, genetic characterization these molecules and their putative role in cancer staging has been elaborated. Prognostic significance of these molecules along with different stages of cancer has also been summarized. Brief outline of ongoing efforts to target hot spot target sites against these VEGFs and their cognate limitations for therapeutic implications are also highlighted.

The Pathophysiologic Roles of TRPM7 Channel

  • Park, Hyun Soo;Hong, Chansik;Kim, Byung Joo;So, Insuk
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.1
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    • pp.15-23
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    • 2014
  • Transient receptor potential melastatin 7 (TRPM7) is a member of the melastatin-related subfamily and contains a channel and a kinase domain. TRPM7 is known to be associated with cell proliferation, survival, and development. It is ubiquitously expressed, highly permeable to $Mg^{2+}$ and $Ca^{2+}$, and its channel activity is negatively regulated by free $Mg^{2+}$ and Mg-complexed nucleotides. Recent studies have investigated the relationships between TRPM7 and a number of diseases. TRPM7 regulates cell proliferation in several cancers, and is associated with ischemic cell death and vascular smooth muscle cell (VSMC) function. This review discusses the physiologic and pathophysiologic functions and significance of TRPM7 in several diseases.

Activation of Lysophosphatidic Acid Receptor Is Coupled to Enhancement of $Ca^{2+}$ -Activated Potassium Channel Currents

  • Choi, Sun-Hye;Lee, Byung-Hwan;Kim, Hyeon-Joong;Hwang, Sung-Hee;Lee, Sang-Mok;Nah, Seung-Yeol
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.3
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    • pp.223-228
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    • 2013
  • The calcium-activated $K^+$ ($BK_{Ca}$) channel is one of the potassium-selective ion channels that are present in the nervous and vascular systems. $Ca^{2+}$ is the main regulator of $BK_{Ca}$ channel activation. The $BK_{Ca}$ channel contains two high affinity $Ca^{2+}$ binding sites, namely, regulators of $K^+$ conductance, RCK1 and the $Ca^{2+}$ bowl. Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is one of the neurolipids. LPA affects diverse cellular functions on many cell types through G protein-coupled LPA receptor subtypes. The activation of LPA receptors induces transient elevation of intracellular $Ca^{2+}$ levels through diverse G proteins such as $G{\alpha}_{q/11}$, $G{\alpha}_i$, $G{\alpha}_{12/13}$, and $G{\alpha}s$ and the related signal transduction pathway. In the present study, we examined LPA effects on $BK_{Ca}$ channel activity expressed in Xenopus oocytes, which are known to endogenously express the LPA receptor. Treatment with LPA induced a large outward current in a reversible and concentration-dependent manner. However, repeated treatment with LPA induced a rapid desensitization, and the LPA receptor antagonist Ki16425 blocked LPA action. LPA-mediated $BK_{Ca}$ channel activation was also attenuated by the PLC inhibitor U-73122, $IP_3$ inhibitor 2-APB, $Ca^{2+}$ chelator BAPTA, or PKC inhibitor calphostin. In addition, mutations in RCK1 and RCK2 also attenuated LPA-mediated $BK_{Ca}$ channel activation. The present study indicates that LPA-mediated activation of the $BK_{Ca}$ channel is achieved through the PLC, $IP_3$, $Ca^{2+}$, and PKC pathway and that LPA-mediated activation of the $BK_{Ca}$ channel could be one of the biological effects of LPA in the nervous and vascular systems.

Circumferential Alignment of Vascular Smooth Muscle Cells in a Cylindrical Microchannel

  • Choi, Jong Seob;Piao, Yunxian;Kim, Kyung Hoon;Seo, Tae Seok
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.08a
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    • pp.274.1-274.1
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    • 2013
  • We report the circumferential alignment of human aortic smooth muscle cells (HASMCs) in an orthogonally micropatterned circular microfluidic channel to form an in vivo-like smooth muscle cell layer. To realize a biomimetic smooth muscle cell layer which is aligned perpendicular to the axis of blood vessel, we first fabricated a half-circular polydimethylsiloxane (PDMS) microchannel by soft lithography using a convex PDMS mold. The orthogonally micro wrinkle patterns were generated inside the half-circular microchannel by stretching-releasing operation under UV irradiation. Upon UV treatment with uniaxial 40 % stretch of a PDMS substrate and releasing process, the microwrinkle patterns perpendicular to the axial direction of the circular microchannel were generated, which could guide the circumferential alignment of HASMCs successfully during cultivation. The analysis of orientation angle, shape index, and contractile protein marker expression indicates that the cultured HASMCs revealed the in vivo-like cell phenotype. Finally, we produced circular microchannels by bonding two half-circular microchannels, and cultured the HASMCs circumferentially with high alignment and viability for 5 days. These results are the first demonstration for constructing an in vivo-like 3D smooth muscle cell layer in the circular microfluidic channel which can provide novel bioassay platforms for in-depth study of HASMC biology and vascular function.

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Analysis of multi-channel photoplethysmograph parameter by the changes of arterial characteries (동맥계 다채널 용적맥파 특징 파라미터 분석에 관한 연구)

  • Han, Soon-Chen;Kim, Hyoung-Jo;Kim, Hyoung-Tae;Kim, Jung-Kuk;Huh, Woong
    • Proceedings of the IEEK Conference
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    • 2003.07c
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    • pp.2745-2748
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    • 2003
  • In this paper, we implement the photoplethysmo-graphy system that have three channel pulse wave detects and one channel ECG amplifier. In order to detect the artery state, we measured the pulse waves at different positions, simultaneously. In general, arterial vascular system suffers the decrease of compliance, increase of resistance, and decrease of distensibility through aging. Therefore, we compared and analyzed variation of tile Pulse waves parameter both in time and frequency domains that is concerned with the changes of arterial characteries. And then evaluated the correlation coefficients between the parameters variation and the age group. As the result of experiment, we found that the Parameters have a significant correlation about aging.

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Alteration of 4-Aminopyridine-Sensitive, Voltage-Dependent $K^+-Channel$ in Arterial Smooth Muscle Cells of One-Kidney, One-Clip Goldblatt Hypertensive Rats

  • Kim, Hoe-Suk;Kim, Se-Hoon;Jeon, Byeong-Hwa;Chang, Seok-Jong
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.5
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    • pp.385-391
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    • 2000
  • Using the patch-clamp technique, we investigated the alteration of 4-aminopyridine(4-AP)-sensitive, voltage-dependent $K^+$ channel (Kv) in the mesenteric arterial smooth muscle cell (MASMC) of renovascular hypertensive model, one-kidney one-clip Goldblatt hypertensive rat (GBH). To isolate $K_V$ current, internal pipette solution contained 5 mM ATP and 10 mM EGTA. Under these condition, MASMC was depolarized by 4-AP, but charybdotoxin did not affect membrane potential. Membrane potential of hypertensive cell $(-40.3{\pm}3.2\;mV)$ was reduced when compared to that of normotensive cell $(-59.5{\pm}2.8\;mV).$ Outward $K^+$ current of hypertensive cell was significantly reduced when compared to normotensive cell. At 60 mV, the outward currents were $19.10{\pm}1.91$ and $14.06{\pm}1.05$ pA/pF in normotensive cell and hypertensive cell respectively. 4-AP-sensitive $K^+$ current was also smaller in hypertensive cell $(4.28{\pm}0.38\;pA/pF)$ than in normotensive cell $(7.65{\pm}0.52\;pA/pF).$ The values of half activation voltage $(V_{1/2})$ and slope factor (k1) as well as the values of half inactivation voltage $(V_{1/2})$ and slope factor (k1) were virtually similar between GBH and NTR. These results suggest that the decrease of 4-AP-sensitive $K^+$ current contributes to a depolarization of membrane potential, which leads to development of vascular tone in GBH.

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Surgical Treatment of Facial Vascular Malformations (안면부 혈관기형 환자의 수술적 처치)

  • Kim, Soung-Min;Park, Jung-Min;Eo, Mi-Young;Myoung, Hoon;Lee, Jong-Ho;Choi, Jin-Young
    • Korean Journal of Cleft Lip And Palate
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    • v.13 no.2
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    • pp.85-92
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    • 2010
  • Vascular malformations (VMs) in the head and neck region are present at birth and grow commensurately with the child, they can result in significant cosmetic problems for the patient, and some may lead to even serious life threatening hemorrhage. Although the molecular mechanisms underlying the formation of these VMs remain unclear, lesions are known to result from abnormal development and morphogenesis. Histologically, there are no evidence of cellular proliferation, but rather progressive dilatation of abnormal channels, which VMs are designated to their prominent channel types such as capillary, venous, lymphatic, arterial, and combined malformations. VMs with an arterial component are rheologically fast-flow, whereas capillary, lymphatic, and venous components are slow-flow. In this article, we review the clinical presentations, diagnosis, and management of VMs of facial regions with author's embolization and surgical treatment cases.

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Tonsillar Lymphangiomatous Polyp in a Dog

  • Choi, Wan-Gyu;Lee, Kwang Sup;Kim, Nak-Hyoung;Yoon, Hasik;Jung, Ji-Youl;Kim, Jae-Hoon
    • Journal of Veterinary Clinics
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    • v.37 no.6
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    • pp.336-338
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    • 2020
  • A 12-year-old female spayed miniature schnauzer with one month history of halitosis had a cylindrical protruding mass about 2 × 2 × 1 cm in size arising from the right palatine tonsil. Histopathologically, tonsillar mass was covered with stratified squamous epithelium and many lymphoid follicles with germinal center were existed in the upper area of submucosa. Numerous variable sized, occasionally cystic dilated vascular channels (thin walled lymphatic channels) lined by flattened, discontinous endothelial cells were widely distributed throughout the core of fibrovascular stroma. According to immunohistochemistry (IHC), lining endothelial cells in vascular channels showed strong immunoreactivities for CD31 and von Willebrand factor. Based on the gross, histopathologic, and IHC findings, the oral mass of dog was diagnosed as tonsillar lymphangiomatous polyp, the second case in a veterinary field.

Shear Stress and Atherosclerosis

  • Heo, Kyung-Sun;Fujiwara, Keigi;Abe, Jun-Ichi
    • Molecules and Cells
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    • v.37 no.6
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    • pp.435-440
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    • 2014
  • Hemodynamic shear stress, the frictional force acting on vascular endothelial cells, is crucial for endothelial homeostasis under normal physiological conditions. When discussing blood flow effects on various forms of endothelial (dys)function, one considers two flow patterns: steady laminar flow and disturbed flow because endothelial cells respond differently to these flow types both in vivo and in vitro. Laminar flow which exerts steady laminar shear stress is atheroprotective while disturbed flow creates an atheroprone environment. Emerging evidence has provided new insights into the cellular mechanisms of flowdependent regulation of vascular function that leads to cardiovascular events such as atherosclerosis, atherothrombosis, and myocardial infarction. In order to study effects of shear stress and different types of flow, various models have been used. In this review, we will summarize our current views on how disturbed flow-mediated signaling pathways are involved in the development of atherosclerosis.

The Role of Intracellular $Mg^{2+}$ in Regulation of $Ca^{2+}-activated$ $K^+$ Channel in Pulmonary Arterial Smooth Muscle Cells of the Rabbit

  • Lee, Suk-Ho;Park, Myoung-Kyu
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.5
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    • pp.611-616
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    • 1998
  • Although the $Ca^{2+}-activated\;K^+\;(I_{K,Ca})$ channel is known to play an important role in the maintenance of resting membrane potential, the regulation of the channel in physiological condition is not completely understood in vascular myocytes. In this study, we investigated the role of cytoplasmic $Mg^{2+}$ on the regulation of $I_{K,Ca}$ channel in pulmonary arterial myocytes of the rabbit using the inside-out patch clamp technique. $Mg^{2+}$ increased open probability (Po), but decreased the magnitude of single channel current. $Mg^{2+}-induced$ block of unitary current showed strong voltage dependence but increase of Po by $Mg^{2+}$ was not dependent on the membrane potential. The apparent effect of $Mg^{2+}$ might, thus, depend on the proportion between opposite effects on the Po and on the conductance of $I_{K,Ca}$ channel. In low concentration of cytoplasmic $Ca^{2+},\;Mg^{2+}$ increased $I_{K,Ca}$ by mainly enhancement of Po. However, at very high concentration of cytoplasmic $Ca^{2+},$ such as pCa 5.5, $Mg^{2+}$ decreased $I_{K,Ca}$ through the inhibition of unitary current. Moreover, $Mg^{2+}$ could activate the channel even in the absence of $Ca^{2+}.\;Mg^{2+}$ might, therefore, partly contribute to the opening of $I_{K,Ca}$ channel in resting membrane potential. This phenomenon might explain why $I_{K,Ca}$ contributes to the resting membrane potential where membrane potential and concentration of free $Ca^{2+}$ are very low.

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