scholarly journals Potassium Channels in the Vascular Diseases

Author(s):  
Yan-Rong Zhu ◽  
Xiao-Xin Jiang ◽  
Peng Ye ◽  
Shao-liang Chen ◽  
Dai-Min Zhang

The vessel wall is an intricate structure composed of three layers: the intima (consisting of endothelial cells), media (consisting of smooth muscle cells and elastic fibers), and externa (consisting of the extracellular matrix scaffold). The homeostasis of the vasculature depends on the consistent function of each layer. In the vascular system, potassium channels are well known to regulate vascular function. The interactions between vascular conditions and membrane potential are complicated. In this chapter, we will focus on the functional regulation of KCa channel, KATP channel, and KV channel in the vascular system. Researchers may continuously obtain insights into the functions of these channels and identify new therapeutic targets for vascular diseases.

2019 ◽  
Vol 8 ◽  
pp. 1549
Author(s):  
Babak Pezeshki ◽  
Ehsan Bahramali ◽  
Amir Ansari ◽  
Aliasghar Karimi ◽  
Mojtaba Frajam ◽  
...  

Background: Diabetes mellitus (DM) is a common metabolic disease worldwide and has many complications. The vascular events are the major complication of DM that have an important effect on mortality and disability. The physical activity (PA) enhances the vascular function by several pathways. The aim of this study was to evaluation of the relationship between PA and vascular diseases in patients with DM.Materials and Methods: This research was performed as the case-control study that was extracted from a prospective epidemiological research study in Iran (PERSIAN). The patients with type 2 DM more than six months defined as case group and the non-DM subjects in control group with ratio 1:2, and both groups were matched in the term of age and sex. The MET score was used to evaluate the level of PA and blood glucose, lipid profile, body mass index, overweight, dyslipidemia, glomerular filtration rate, myocardial infarction (MI), unstable angina, and stroke.Results: Overall, 1242 patients with DM were extracted, and 2484 non-diabetic subjects were investigated. In the case group, 355(28.6 %) and 887(71.4%) were men and women, respectively, the and 710 (28.6%) men and 1774(71.4%) women in control group. The mean MET score was 30 and 40.97 in the DM and non-DM groups, respectively (P˂0.001). The frequency of MI, stroke, and cardiac ischemia were 44 (3.5%), 37 (3%), and 267 (21.5%), respectively in DM group, and 54 (2.2%), 43 (1.7%), and 389 (15.7%), respectively in non-DM group.Conclusion: The incidence of vascular events associated with PA level in patients with DM and adherence to regular PA reduce the vascular events and DM complications. [GMJ.2019;inpress:e1549]


Function ◽  
2021 ◽  
Author(s):  
Nick Weir ◽  
Thomas A Longden

Abstract A Perspective on "Traumatic Brain Injury Impairs Systemic Vascular Function Through Disruption of Inward-Rectifier Potassium Channels"


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Javier I. Ottaviani ◽  
Abigail Britten ◽  
Debora Lucarelli ◽  
Robert Luben ◽  
Angela A. Mulligan ◽  
...  

Abstract Flavan-3-ols are a group of bioactive compounds that have been shown to improve vascular function in intervention studies. They are therefore of great interest for the development of dietary recommendation for the prevention of cardio-vascular diseases. However, there are currently no reliable data from observational studies, as the high variability in the flavan-3-ol content of food makes it difficult to estimate actual intake without nutritional biomarkers. In this study, we investigated cross-sectional associations between biomarker-estimated flavan-3-ol intake and blood pressure and other CVD risk markers, as well as longitudinal associations with CVD risk in 25,618 participants of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort. High flavan-3-ol intake, achievable as part of an habitual diet, was associated with a significantly lower systolic blood pressure (− 1.9 (− 2.7; − 1.1) mmHg in men and − 2.5 (− 3.3; − 1.8) mmHg in women; lowest vs highest decile of biomarker), comparable to adherence to a Mediterranean Diet or moderate salt reduction. Subgroup analyses showed that hypertensive participants had stronger inverse association between flavan-3-ol biomarker and systolic blood pressure when compared to normotensive participants. Flavanol intake could therefore have a role in the maintenance of cardiovascular health on a population scale.


2017 ◽  
Vol 123 (6) ◽  
pp. 1708-1720 ◽  
Author(s):  
Jayson R. Gifford ◽  
Russell S. Richardson

As dysfunction of the vascular system is an early, modifiable step in the progression of many cardiovascular diseases, there is demand for methods to monitor the health of the vascular system noninvasively in clinical and research settings. Validated by very good agreement with more technical assessments of vascular function, like intra-arterial drug infusions and flow-mediated dilation, the passive leg movement (PLM) technique has emerged as a powerful, yet relatively simple, test of peripheral vascular function. In the PLM technique, the change in leg blood flow elicited by the passive movement of the leg through a 90° range of motion is quantified with Doppler ultrasound. This relatively easy-to-learn test has proven to be ≤80% dependent on nitric oxide bioavailability and is especially adept at determining peripheral vascular function across the spectrum of cardiovascular health. Indeed, multiple reports have documented that individuals with decreased cardiovascular health such as the elderly and those with heart failure tend to exhibit a substantially blunted PLM-induced hyperemic response (~50 and ~85% reduction, respectively) compared with populations with good cardiovascular health such as young individuals. As specific guidelines have not yet been put forth, the purpose of this Cores of Reproducibility in Physiology (CORP) article is to provide a comprehensive reference for the assessment and interpretation of vascular function with PLM with the aim to increase reproducibility and consistency among studies and facilitate the use of PLM as a research tool with clinical relevance.


2000 ◽  
Vol 278 (2) ◽  
pp. H515-H520 ◽  
Author(s):  
Jill M. Wecht ◽  
Ronald E. de Meersman ◽  
Joseph P. Weir ◽  
William A. Bauman ◽  
David R. Grimm

The effects of autonomic disruption and inactivity were studied on the venous vascular system. Forty-eight subjects, 24 with spinal cord injury (SCI) and 12 sedentary and 12 active able-bodied controls, participated in this study. Peripheral autonomic data were obtained to estimate sympathetic vasomotor control [low-frequency component of systolic blood pressure (LFSBP)]. Vascular parameters were determined using strain-gauge venous occlusion plethysmography: venous capacitance (VC), venous emptying rate (VER), and total venous outflow (VOt). An additional vascular parameter was calculated: venous compliance [(VC/occlusion pressure) × 100]. VC and VOt were significantly different (SCI < sedentary < active). VER adjusted for VC was not different for any group comparison, whereas venous compliance was significantly lower in the SCI group than in the able-bodied groups and in the sedentary group compared with the active group. Regression analysis for the total group revealed a significant relationship between LFSBP and venous compliance ( r = 0.64, P < 0.0001). After controlling for LFSBP through analysis of covariance, we found that mean differences for all venous vascular parameters did not change from unadjusted mean values. Our findings suggest that in subjects with SCI, the loss of sympathetic vasomotor tone contributes more than inactivity to reductions in venous vascular function. Heightened VC, VOt, vasomotor tone, and venous compliance in the active group compared with the sedentary group imply that regular endurance training contributes to optimal venous vascular function and peripheral autonomic integrity.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Rita C. Tostes ◽  
R. Clinton Webb

The endothelium plays a pivotal role in vascular homeostasis, and endothelial dysfunction is a major feature of cardiovascular diseases, such as arterial hypertension, atherosclerosis, and diabetes. Recently, uridine adenosine tetraphosphate (Up4A) has been identified as a novel and potent endothelium-derived contracting factor (EDCF). Up4A structurally contains both purine and pyrimidine moieties, which activate purinergic receptors. There is an accumulating body of evidence to show that Up4A modulates vascular function by actions on endothelial and smooth muscle cells. In this paper, we discuss the effects of Up4A on vascular function and a potential role for Up4A in cardiovascular diseases.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yaoyao Cai ◽  
Haipeng Yao ◽  
Zhen Sun ◽  
Ying Wang ◽  
Yunyun Zhao ◽  
...  

Nuclear factor of activated T cells (NFAT) is a transcription factor with a multidirectional regulatory function, that is widely expressed in immune cells, including cells in the cardiovascular system, and non-immune cells. A large number of studies have confirmed that calcineurin/NFAT signal transduction is very important in the development of vascular system and cardiovascular system during embryonic development, and plays some role in the occurrence of vascular diseases such as atherosclerosis, vascular calcification, and hypertension. Recent in vitro and in vivo studies have shown that NFAT proteins and their activation in the nucleus and binding to DNA-related sites can easily ɨnduce the expression of downstream target genes that participate in the proliferation, migration, angiogenesis, and vascular inflammation of vascular wall related cells in various pathophysiological states. NFAT expression is regulated by various signaling pathways, including CD137-CD137L, and OX40-OX40L pathways. As a functionally diverse transcription factor, NFAT interacts with a large number of signaling molecules to modulate intracellular and extracellular signaling pathways. These NFAT-centered signaling pathways play important regulatory roles in the progression of atherosclerosis, such as in vascular smooth muscle cell phenotypic transition and migration, endothelial cell injury, macrophage-derived foam cell formation, and plaque calcification. NFAT and related signaling pathways provide new therapeutic targets for vascular diseases such as atherosclerosis. Hence, further studies of the mechanism of NFAT in the occurrence and evolution of atherosclerosis remain crucial.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yuichi Kimura ◽  
Yasuhiro Izumiya ◽  
Satoshi Araki ◽  
Satoru Yamamura ◽  
Yoshiro Onoue ◽  
...  

Introduction: Aging is a well-established cardiovascular risk factor and associated with vascular dysfunction. Sirt7, one of the members of mammalian sirtuin family, is thought to be involved in age-related diseases. However, little is known about the relative contribution of Sirt7 in vascular dysfunction. Hypothesis: Sirt7 maintains vascular cell functions and its deficiency plays a critical role in vascular diseases. Methods: Sirt7 loss- and gain-of-function experiments were performed with human aortic smooth muscle cells (HAoSMCs) and human umbilical vein endothelial cells (HUVECs). In vivo, blood flow recovery was evaluated by hindlimb ischemia model in homozygous Sirt7 deficient (Sirt7-/-) and wild-type (WT) mice. Irradiated WT mice were intravenously received bone marrow (BM) cells from WT or Sirt7 -/- mouse to achieve BM transfer. Results: An RNAi-medicated Sirt7 knockdown resulted in a significant inhibition of HAoSMCs proliferation following serum or Platelet-derived growth factor BB (PDGF-BB) stimulation as determined by cell count, BrdU cell proliferation assay and MTS proliferation assay. Knockdown of endogenous Sirt7 also reduced cell migration as revealed by Boyden chamber migration assay. The Cyclin D1 and Cyclin dependent kinase 2 (CDK2) protein levels were significantly decreased in Sirt7 siRNA-treated HAoSMCs in response to serum or PDGF-BB stimulation. In endothelial cells, knockdown of Sirt7 attenuated tube formation, proliferation and migration. These changes were accompanied by reduced ERK activation and VCAM-1 mRNA and protein expression in Sirt7 siRNA-treated HUVECs. Conversely, overexpression of Sirt7 by adenovirus enhanced tube formation and cell proliferation. In vivo, blood flow recovery in response to hindlimb ischemia was significantly attenuated in Sirt7-/- mice compared with WT mice. There was no difference in blood flow recovery between WT mice transplanted with WT or Sirt7-/- BM cells suggesting that Sirt7 deficiency in vascular cells have a predominant effect on attenuated blood flow recovery in response to hindlimb ischemia. Conclusions: Sirt7 in blood vessel components have an important role in maintenance of vascular function. Sirt7 could be a promising therapeutic target for vascular diseases.


1998 ◽  
Vol 7 (2) ◽  
pp. 131-140 ◽  
Author(s):  
J McHugh ◽  
DJ Cheek

The endothelial cells of the vascular system are responsible for many biological activities that maintain vascular homeostasis. Responding to a variety of chemical and physical stimuli, the endothelium elaborates a host of vasoactive agents. One of these agents, endothelium-derived relaxing factor, now accepted as nitric oxide, influences both cellular constituents of the blood and vascular smooth muscle. A principal intracellular target for nitric oxide is guanylate cyclase, which, when activated, increases the intracellular concentration of cyclic guanosine monophosphate, which in turn activates protein kinase G. Acting by this pathway, nitric oxide induces relaxation of vascular smooth muscle and inhibits platelet activation and aggregation. Derangements in endothelial production of nitric oxide are implicated as both cause and consequence of vascular diseases, including hypertension, atherosclerosis, and coronary artery disease.


2014 ◽  
Vol 144 (5) ◽  
pp. 457-467 ◽  
Author(s):  
Sandipan Chowdhury ◽  
Benjamin M. Haehnel ◽  
Baron Chanda

Voltage-dependent potassium channels play a crucial role in electrical excitability and cellular signaling by regulating potassium ion flux across membranes. Movement of charged residues in the voltage-sensing domain leads to a series of conformational changes that culminate in channel opening in response to changes in membrane potential. However, the molecular machinery that relays these conformational changes from voltage sensor to the pore is not well understood. Here we use generalized interaction-energy analysis (GIA) to estimate the strength of site-specific interactions between amino acid residues putatively involved in the electromechanical coupling of the voltage sensor and pore in the outwardly rectifying KV channel. We identified candidate interactors at the interface between the S4–S5 linker and the pore domain using a structure-guided graph theoretical approach that revealed clusters of conserved and closely packed residues. One such cluster, located at the intracellular intersubunit interface, comprises three residues (arginine 394, glutamate 395, and tyrosine 485) that interact with each other. The calculated interaction energies were 3–5 kcal, which is especially notable given that the net free-energy change during activation of the Shaker KV channel is ∼14 kcal. We find that this triad is delicately maintained by balance of interactions that are responsible for structural integrity of the intersubunit interface while maintaining sufficient flexibility at a critical gating hinge for optimal transmission of force to the pore gate.


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