Persistent mechanical stretch-induced calcium overload and MAPK signal activation contributed to SCF reduction in colonic smooth muscle in vivo and in vitro

Background/Aims: Physiological mechanical stretch in vivo helps to maintain the quiescent contractile differentiation of vascular smooth muscle cells (VSMCs), but the underlying mechanisms are still unclear. Here, we investigated the effects of SIRT1 in VSMC differentiation in response to mechanical cyclic stretch. Methods and Results: Rat VSMCs were subjected to 10%-1.25Hz-cyclic stretch in vitro using a FX-4000T system. The data indicated that the expression of contractile markers, including α-actin, calponin and SM22α, was significantly enhanced in VSMCs that were subjected to cyclic stretch compared to the static controls. The expression of SIRT1 and FOXO3a was increased by the stretch, but the expression of FOXO4 was decreased. Decreasing SIRT1 by siRNA transfection attenuated the stretch-induced expression of contractile VSMC markers and FOXO3a. Furthermore, increasing SIRT1 by either treatment with activator resveratrol or transfection with a plasmid to induce overexpression increased the expression of FOXO3a and contractile markers, and decreased the expression of FOXO4 in VSMCs. Similar trends were observed in VSMCs of SIRT1 (+/-) knockout mice. The overexpression of FOXO3a promoted the expression of contractile markers in VSMCs, while the overexpression of FOXO4 demonstrated the opposite effect. Conclusion: Our results indicated that physiological cyclic stretch promotes the contractile differentiation of VSMCs via the SIRT1/FOXO pathways and thus contributes to maintaining vascular homeostasis.

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Stretch-dependent (myogenic) tone in rabbit ear resistance arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1986.250.1.h87 ◽

1986 ◽

Vol 250 (1) ◽

pp. H87-H95 ◽

Cited By ~ 13

Author(s):

J. J. Hwa ◽

J. A. Bevan

Keyword(s):

Smooth Muscle ◽

Vascular Tone ◽

Mechanical Stretch ◽

Myogenic Tone ◽

Resistance Arteries ◽

Physiological Regulation ◽

Rabbit Ear ◽

Arterial Tone

Rabbit ear resistance arteries are vessels with three to six layers of smooth muscle cells and an unstretched lumen diameter of 75-150 micron. Ring segments of these arteries, in response to mechanical stretch in vitro, developed a maintained tonic contraction. The stretch-dependent contraction achieved a plateau within 10-30 min. Smooth muscle relaxants, such as NaNO2 and papaverine, substitution of extracellular Ca2+ by subthreshold Ca2+ (25 microM), or exposure to the Ca2+ influx antagonist Mn2+ abolished the stretch-dependent tone. The extent of the tone was dependent on the level of the applied stretch and the extracellular Ca2+ concentration ( [Ca2+]o). The maximal tone developed at optimal stretch, and [Ca2+]o in the bath solution was 18.1 +/- 4.6% of the maximal contraction of the vessel to histamine. This level of tone is comparable to neurogenic tone developed in response to nerve stimulation within the physiological frequency range. The stretch-dependent tone is considered probably myogenic in origin, since it was present in arterial segments that had been chronically denervated by surgical sympathectomy, mechanically deprived of the endothelium, and multireceptor blocked (phenoxybenzamine, 10(-6) M). Our findings suggest first that the stretch-dependent tone is myogenic and may be similar to basal vascular tone arising from the stretch of arterial pressure and its changes in vivo. Second, the magnitude of myogenic tone is a function of the applied stretch and the [Ca2+]o. Finally, myogenic tone is important in the physiological regulation of arterial tone in the rabbit ear resistance arteries.

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In vitro desmin assembly and in vivo changes in developing smooth muscle

10.31274/rtd-180813-12384 ◽

1991 ◽

Author(s):

Rong-Ghi Robert Chou

Keyword(s):

Smooth Muscle

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Faculty Opinions recommendation of MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3171956.2871056 ◽

2010 ◽

Author(s):

Irina Kaverina ◽

Paul Miller

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells

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Targeting Matrix Metalloproteinases in Atherosclerosis and Cardiovascular Dysfunction

Revista de Chimie ◽

10.37358/rc.19.2.6992 ◽

2019 ◽

Vol 70 (2) ◽

pp. 718-720

Author(s):

Lucia Corina Dima-Cozma ◽

Sebastian Cozma ◽

Delia Hinganu ◽

Cristina Mihaela Ghiciuc ◽

Florin Mitu

Keyword(s):

Smooth Muscle ◽

Matrix Metalloproteinases ◽

Cholesterol Synthesis ◽

Balloon Dilation ◽

Aortic Aneurysms ◽

Arterial Lesions ◽

Smooth Muscle Cell Migration ◽

And Migration

Matrix metalloproteinases (MMPs) are the primary mediators of extracellular remodeling and their properties are useful in diagnostic evaluation and treatment. They are zinc-dependent proteases. MMPs have been involved in the mechanisms of atherosclerosis in various arterial areas, ischemic heart disease and myocardial infarction, atrial fibrillation and aortic aneurysms. Recently, MMP9 has been implicated in dyslipidemia and cholesterol synthesis by the liver. Increased MMP expression and activity has been associated with neointimal arterial lesions and migration of smooth muscle cells after arterial balloon dilation, while MMP inhibition decreases smooth muscle cell migration in vivo and in vitro.

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Inhibition of dihydropyridine-sensitive calcium entry in hypoxic relaxation of airway smooth muscle

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1995.268.2.l201 ◽

1995 ◽

Vol 268 (2) ◽

pp. L201-L206 ◽

Cited By ~ 2

Author(s):

C. Vannier ◽

T. L. Croxton ◽

L. S. Farley ◽

C. A. Hirshman

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Muscle Tone ◽

Bay K 8644 ◽

O2 Concentration ◽

Voltage Dependent ◽

Progressive Hypoxia ◽

Carbamyl Choline

Hypoxia dilates airways in vivo and reduces active tension of airway smooth muscle in vitro. To determine whether hypoxia impairs Ca2+ entry through voltage-dependent channels (VDC), we tested the ability of dihydropyridines to modulate hypoxia-induced relaxation of KCl- and carbamyl choline (carbachol)-contracted porcine bronchi. Carbachol- or KCl-contracted bronchial rings were exposed to progressive hypoxia in the presence or absence of 1 microM BAY K 8644 (an L-type-channel agonist). In separate experiments, rings were contracted with carbachol or KCl, treated with nifedipine (a VDC antagonist), and finally exposed to hypoxia. BAY K 8644 prevented hypoxia-induced relaxation in KCl-contracted bronchi. Nifedipine (10(-5) M) totally relaxed KCl- contracted bronchi. Carbachol-contracted bronchi were only partially relaxed by nifedipine but were completely relaxed when the O2 concentration of the gas was reduced from 95 to 0%. These data indicate that hypoxia can reduce airway smooth muscle tone by limiting entry of Ca2+ through a dihydropyridine-sensitive pathway, but that other mechanisms also contribute to hypoxia-induced relaxation of carbachol-contracted bronchi.

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ApoE4 (Δ272–299) induces mitochondrial‐associated membrane formation and mitochondrial impairment by enhancing GRP75-modulated mitochondrial calcium overload in neuron

Cell & Bioscience ◽

10.1186/s13578-021-00563-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tao Liang ◽

Weijian Hang ◽

Jiehui Chen ◽

Yue Wu ◽

Bin Wen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Er Stress ◽

Mitochondrial Dysfunction ◽

Mitochondrial Function ◽

Calcium Transport ◽

Calcium Overload ◽

Mitochondrial Calcium ◽

Mitochondrial Impairment

Abstract Background Apolipoprotein E4 (apoE4) is a major genetic risk factor of Alzheimer’s disease. Its C-terminal-truncated apoE4 (Δ272–299) has neurotoxicity by affecting mitochondrial respiratory function. However, the molecular mechanism(s) underlying the action of apoE4 (Δ272–299) in mitochondrial function remain poorly understood. Methods The impact of neuronal apoE4 (Δ272–299) expression on ER stress, mitochondrial-associated membrane (MAM) formation, GRP75, calcium transport and mitochondrial impairment was determined in vivo and in vitro. Furthermore, the importance of ER stress or GRP75 activity in the apoE4 (Δ272–299)-promoted mitochondrial dysfunction in neuron was investigated. Results Neuronal apoE4 (Δ272–299) expression induced mitochondrial impairment by inducing ER stress and mitochondrial-associated membrane (MAM) formation in vivo and in vitro. Furthermore, apoE4 (Δ272–299) expression promoted GRP75 expression, mitochondrial dysfunction and calcium transport into the mitochondria in neuron, which were significantly mitigated by treatment with PBA (an inhibitor of ER stress), MKT077 (a specific GRP75 inhibitor) or GRP75 silencing. Conclusions ApoE4 (Δ272–299) significantly impaired neuron mitochondrial function by triggering ER stress, up-regulating GRP75 expression to increase MAM formation, and mitochondrial calcium overload. Our findings may provide new insights into the neurotoxicity of apoE4 (Δ272–299) against mitochondrial function and uncover new therapeutic targets for the intervention of Alzheimer’s disease.

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Effects of Hyperglycemia on Vascular Smooth Muscle Ca2+Signaling

BioMed Research International ◽

10.1155/2017/3691349 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 6

Author(s):

Nahed El-Najjar ◽

Rashmi P. Kulkarni ◽

Nancy Nader ◽

Rawad Hodeify ◽

Khaled Machaca

Keyword(s):

Insulin Resistance ◽

Smooth Muscle ◽

Sarcoplasmic Reticulum ◽

Vascular Smooth Muscle ◽

Complex Disease ◽

Prolonged Exposure ◽

In Vitro System ◽

A7r5 Cells

Diabetes is a complex disease that is characterized with hyperglycemia, dyslipidemia, and insulin resistance. These pathologies are associated with significant cardiovascular implications that affect both the macro- and microvasculature. It is therefore important to understand the effects of various pathologies associated with diabetes on the vasculature. Here we directly test the effects of hyperglycemia on vascular smooth muscle (VSM) Ca2+signaling in an isolated in vitro system using the A7r5 rat aortic cell line as a model. We find that prolonged exposure of A7r5 cells to hyperglycemia (weeks) is associated with changes to Ca2+signaling, including most prominently an inhibition of the passive ER Ca2+leak and the sarcoplasmic reticulum Ca2+-ATPase (SERCA). To translate these findings to the in vivo condition, we used primary VSM cells from normal and diabetic subjects and find that only the inhibition of the ER Ca2+leaks replicates in cells from diabetic donors. These results show that prolonged hyperglycemia in isolation alters the Ca2+signaling machinery in VSM cells. However, these alterations are not readily translatable to the whole organism situation where alterations to the Ca2+signaling machinery are different.

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