Ca2+ handling alterations and vascular dysfunction in diabetes

Fernández‐Velasco, María; Ruiz‐Hurtado, Gema; Gómez, Ana M.; Rueda, Angélica

doi:10.1016/j.ceca.2014.08.007

Cited by 35 publications

(44 citation statements)

References 140 publications

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“…Ca 2+ is a well-known second messenger that regulates a wide range of cell functions including excitation-contraction coupling, excitation-secretion coupling, gene transcription, cell growth, differentiation, apoptosis, membrane fusion, and ion channel activation [8–11]. Previous studies reported that lysoPC induced an sustained increase in intracellular free Ca 2+ (Ca 2+ i ) in human [12] and rabbit [13] coronary artery SMCs and in human umbilical vein endothelial cells [14] and in cultured human corporal SMCs [15].…”

Section: Introductionmentioning

confidence: 99%

TRPC1/TRPC3 channels mediate lysophosphatidylcholine-induced apoptosis in cultured human coronary artery smooth muscles cells

Wang

2016

Oncotarget

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The earlier study showed that lysophosphatidylcholine (lysoPC) induced apoptosis in human coronary artery smooth muscle cells (SMCs); however, the related molecular mechanisms are not fully understood. The present study investigated how lysoPC induces apoptosis in cultured human coronary artery SMCs using cell viability assay, flow cytometry, confocal microscopy, and molecular biological approaches. We found that lysoPC reduced cell viability in human coronary artery SMCs by eliciting a remarkable Ca2+ influx. The effect was antagonized by La3+, SKF-96365, or Pyr3 as well as by silencing TRPC1 or TRPC3. Co-immunoprecipitation revealed that TRPC1 and TRPC3 had protein-protein interaction. Silencing TRPC1 or TRPC3 countered the lysoPC-induced increase of Ca2+ influx and apoptosis, and the pro-apoptotic proteins Bax and cleaved caspase-3 and decrease of the anti-apoptotic protein Bcl-2 and the survival kinase pAkt. These results demonstrate the novel information that TRPC1/TRPC3 channels mediate lysoPC-induced Ca2+ influx and apoptosis via activating the pro-apoptotic proteins Bax and cleaved caspase-3 and inhibiting the anti-apoptotic protein Bcl-2 and the survival kinase pAkt in human coronary artery SMCs, which implies that TRPC1/TRC3 channels may be the therapeutic target of lysoPC-induced disorders such as atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

TRPC1/TRPC3 channels mediate lysophosphatidylcholine-induced apoptosis in cultured human coronary artery smooth muscles cells

Wang

2016

Oncotarget

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“…Abnormal intracellular Ca 2+ handling resulting from a defect in SR function is a leading cause of cardiovascular disease [22–25]. Impaired Ca 2+ uptake by the SR is mainly due to a decrease in SERCA2a activity that can be caused by changes in its expression and/or post-translational modification [26–28].…”

Section: Discussionmentioning

confidence: 99%

A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells

Jang

Kang

et al. 2016

PLoS ONE

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Neointimal growth in the injured vasculature is largely facilitated by the proliferation of vascular smooth muscle cells (VSMC), which associates with reduced sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. The gene transfer-mediated restoration of the SERCA2a level thus attenuates neointimal growth and VSMC proliferation. We previously reported that a peptide targeted to protein phosphatase 1, ψPLB-SE, normalizes SERCA2a activity in cardiomyocytes. In this study, we found that ψPLB-SE attenuated neointimal growth in balloon-injured rat carotid arteries, and the proliferation and migration of VSMC cultured in high-serum media (synthetic conditions). In parallel, ψPLB-SE inhibited the degradation of SERCA2a in the injured carotid arteries and VSMC under synthetic conditions. The calpain inhibitor MDL28170 also attenuated SERCA2a degradation and VSMC proliferation under synthetic conditions, indicating that calpain degrades SERCA2a. The Ca2+ ionophore A23187 induced SERCA2a degradation in VSMC, which was blocked by either ψPLB-SE or MDL28170. Additionally, ψPLB-SE normalized the cytosolic Ca2+ level in VSMC that was increased by either A23187 or synthetic stimulation. Collectively, these data indicate that ψPLB-SE corrects the abnormal Ca2+ handling by activating SERCA2a, which further protects SERCA2a from calpain-dependent degradation in VSMC. We conclude that ψPLB-SE may form the basis of a therapeutic strategy for vascular proliferative disorders.

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“…Diabetic vascular complication is usually characterized by the increased vascular resistance, augmented contractile activity, impaired endothelium-dependent vasodilatation, increased oxidative stress, enhanced inflammation, and progressive atherosclerosis [1, 2]. The clustering of risk factors could accelerate the progression of diabetic vascular complication, such as hyperglycemia, high blood pressure, dyslipidaemia, insulin resistance, smoking, and obesity.…”

Section: Introductionmentioning

confidence: 99%

“…Particularly, increases in intracellular Ca 2+ from receptor- or ion channel-activated pathways are the primary triggers to activate myosin light chain kinase (MLCK), which phosphorylates myosin light chains (MLC) and then activating myosin ATPase and leading to vascular contraction. It is considered that arterial contractility and vascular tone are predominantly controlled by membrane potential and Ca 2+ influx via long-lasting voltage-dependent Ca 2+ ( l -type, Ca L ) of VSMCs [1, 22]. Evidences from human and animal studies indicated that diabetic vascular complication with elevated blood pressure is tightly coupled to the impaired Ca L channels in VSMCs [1, 23].…”

Section: Introductionmentioning

confidence: 99%

“…It is considered that arterial contractility and vascular tone are predominantly controlled by membrane potential and Ca 2+ influx via long-lasting voltage-dependent Ca 2+ ( l -type, Ca L ) of VSMCs [1, 22]. Evidences from human and animal studies indicated that diabetic vascular complication with elevated blood pressure is tightly coupled to the impaired Ca L channels in VSMCs [1, 23]. Therefore, Ca L channel and its downstream molecules could be the important therapeutic targets in diabetic vascular complications [1].…”

Section: Introductionmentioning

confidence: 99%

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Salidroside contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic Goto-Kakizaki Rats by inhibition of L-type calcium channel in smooth muscle cells

Jun-wei

Bai

et al. 2017

BMC Pharmacol Toxicol

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BackgroundVascular disease is a common and often severe complication in diabetes mellitus. Hyperglycemia and hypertension are considered to be two of the leading risk factors for vascular complications in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and blood pressure in diabetic patients at the same time. Salidroside (SAL) is the major active ingredient derived from Rhodiola. Recently, it has been reported that SAL have an obvious hypoglycemic effect in diabetes and show a beneficial activity in diabetic vascular dysfunction. However, it remains unknown whether or not SAL treatment could directly reduce blood pressure in diabetes. Furthermore, it is not clear what is the molecular mechanism underlying the vascular protection of SAL treatment in diabetes.MethodsMale diabetic Goto-Kakizaki (GK) and non-diabetic control Wistar-Kyoto (WKY) rats were administrated with different dosages of SAL (50, 100 and 200 mg/kg/day) for 4 weeks. Contractile responsiveness of cerebral artery to KCl or 5-HT was investigated by Pressure Myograph System. The activity of CaL channel was investigated by recording whole-cell currents, assessing the expressions of CaL channel α1C-subunit and its downstream kinase, MLCK, at protein or mRNA levels.ResultsWe showed that administration of 100 mg/kg/day SAL for 4 weeks not only lowered blood glucose, but also reduced blood pressure and alleviated cerebrovascular contractile activity in diabetic GK rats, which suggested that SAL treatment may provide a combinational therapy for lowering blood glucose and reducing blood pressure in diabetes at the same time. Furthermore, SAL treatment markedly inhibited the function and expression of CaL channel in cerebral VSMCs isolated from diabetic GK rats or when exposed to hyperglycemia condition, which may be the underlying mechanism responsible for the vascular protection of SAL in diabetes.ConclusionsThe present study provided evidences that SAL contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic GK rats by inhibition of CaL channel in smooth muscle cells, which may provide a novel approach to treat vascular complications in diabetic patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-017-0135-8) contains supplementary material, which is available to authorized users.

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Ca2+ handling alterations and vascular dysfunction in diabetes

Cited by 35 publications

References 140 publications

TRPC1/TRPC3 channels mediate lysophosphatidylcholine-induced apoptosis in cultured human coronary artery smooth muscles cells

TRPC1/TRPC3 channels mediate lysophosphatidylcholine-induced apoptosis in cultured human coronary artery smooth muscles cells

A Decoy Peptide Targeted to Protein Phosphatase 1 Attenuates Degradation of SERCA2a in Vascular Smooth Muscle Cells

Salidroside contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic Goto-Kakizaki Rats by inhibition of L-type calcium channel in smooth muscle cells

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