scholarly journals PDE-Mediated Cyclic Nucleotide Compartmentation in Vascular Smooth Muscle Cells: From Basic to a Clinical Perspective

2021 ◽  
Vol 9 (1) ◽  
pp. 4
Author(s):  
Margarida Lorigo ◽  
Nelson Oliveira ◽  
Elisa Cairrao
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Cyclic Nucleotide ◽  
Muscle Cells ◽  
Mortality And Morbidity ◽  
Vascular Smcs ◽  
Novel Drugs ◽  
Causes Of Mortality

Cardiovascular diseases are important causes of mortality and morbidity worldwide. Vascular smooth muscle cells (SMCs) are major components of blood vessels and are involved in physiologic and pathophysiologic conditions. In healthy vessels, vascular SMCs contribute to vasotone and regulate blood flow by cyclic nucleotide intracellular pathways. However, vascular SMCs lose their contractile phenotype under pathological conditions and alter contractility or signalling mechanisms, including cyclic nucleotide compartmentation. In the present review, we focus on compartmentalized signaling of cyclic nucleotides in vascular smooth muscle. A deeper understanding of these mechanisms clarifies the most relevant axes for the regulation of vascular tone. Furthermore, this allows the detection of possible changes associated with pathological processes, which may be of help for the discovery of novel drugs.

Abstract 496: Extracellular Matrix Secretion by Vascular Smooth Muscle Cells: Role of MiR-195 and MiR-29b

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Anna Zampetaki ◽  
Xiaoke Yin ◽  
Ursula Mayr ◽  
Renata Gomes ◽  
Sarah Langley ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Vascular Smcs

Rationale: Extracellular matrix (ECM) remodeling is a key function of vascular smooth muscle cells (SMCs). MicroRNAs (miRNAs), in particular the miR-29 family and miR-195, have been implicated in the control of ECM secretion. Objective: To perform a proteomics comparison of miRNA effects on ECM production by vascular SMCs. Methods and Results: Murine SMCs were transfected with miRNA mimics and antimiRs of miR-29b and miR-195, and their conditioned medium was analyzed by mass spectrometry. Both miRNAs targeted a cadre of ECM proteins, including proteoglycans, collagens, proteases, elastin and proteins associated with elastic microfibrils, albeit miR-29 showed a stronger effect. The proteomics findings were subsequently validated at the transcription level using quantitative polymerase chain reaction. Similar to miR-29, in vivo inhibition of miR-195 by intraperitoneal injection of cholesterol bound antagomiRs led to significant alterations of elastin expression in murine aortas. Since elastin degradation is a key event in aortic aneurysm formation, we investigated miR-195 expression in patients. In human aortic aneurysmal tissue, miR-195 expression was reduced compared to non-aneurysmal tissue. In plasma, a comparison between male patients with abdominal aortic aneurysms and controls matched for diabetes and hypertension returned a panel of five highly correlated miRNAs: miR-195, miR-125b, miR-148a, miR-20a and miR-340 showed significant inverse associations with the presence of abdominal aortic aneurysms and aortic diameter, with miR-195 dominating in terms of association strength. Conclusions: Using proteomic analysis, we compared the effect of miR-29 and miR-195 on ECM secretion by vascular SMCs and identified novel miRNA targets. Findings in patients support an important role for miR-195 in vascular remodeling as evidenced by reduced miR-195 expression in human aneurysmal tissue and an inverse correlation between plasma miR-195 levels and aortic diameter.

Antiapoptotic Action of Carbon Monoxide on Cultured Vascular Smooth Muscle Cells

2003 ◽  
Vol 228 (5) ◽  
pp. 572-575 ◽  
Author(s):  
Xiao-Ming Liu ◽  
Gary B. Chapman ◽  
Kelly J. Peyton ◽  
Andrew I. Schafer ◽  
William Durante
Keyword(s):  
Carbon Monoxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Kinase Inhibitor ◽  
Critical Role ◽  
Muscle Cells ◽  
Mitogen Activated Protein Kinase ◽  
Vascular Smcs

Vascular smooth muscle cells (SMCs) generate carbon monoxide (CO) from the degradation of heme by the enzyme heme oxygenase. Because recent studies indicate that CO influences the properties of vascular SMCs, we examined whether this diatomic gas regulates apoptosis in vascular SMCs. Treatment of cultured rat aortic SMCs with a cytokine cocktail consisting of interleukin-1β (5 ng/ml), tumor necrosis factor-α (20 ng/ml), and interferon-γ (200 U/ml) for 48 hr stimulated apoptosis, as demonstrated by DNA laddering, caspase-3 activation, and annexin V staining. However, the exogenous addition of CO (200 ppm) completely blocked cytokine-mediated apoptosis. The antiapoptotic action of CO was partially reversed by the soluble guanylate cyclase inhibitor, H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μM). In contrast, the p38 mitogen-activated protein kinase inhibitor, SB203580 (10 μM), had no effect on SMC apoptosis. These findings indicate that CO is a potent inhibitor of vascular SMC apoptosis and that it blocks apoptosis, in part, by activating the cGMP signaling pathway. The ability of CO to inhibit vascular SMC apoptosis may play a critical role in attenuating lesion formation at sites of arterial damage.

Reduced Na-K-Cl cotransport in vascular smooth muscle cells from spontaneously hypertensive rats

1988 ◽  
Vol 255 (2) ◽  
pp. C169-C180 ◽  
Author(s):  
M. E. O'Donnell ◽  
N. E. Owen
Keyword(s):  
Smooth Muscle ◽  
Essential Hypertension ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Cyclic Nucleotide ◽  
Spontaneously Hypertensive Rats ◽  
Muscle Cells ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

We have previously demonstrated the presence of a prominent, cyclic nucleotide-sensitive Na-K-Cl cotransport in vascular smooth muscle cells (VSMC). Others have observed that Na-K-Cl cotransport levels are reduced in erythrocytes of patients with essential hypertension and have proposed that a defect in this Na transport system may play a role in the pathogenesis of the disease. However, such a defect has not been demonstrated in the putative target tissue for essential hypertension, i.e., the VSMC. In the present study, we compared Na-K-Cl cotransport of VSMC from spontaneously hypertensive rats (SHR) with Na-K-Cl cotransport of VSMC from normotensive Wistar-Kyoto rats (WKY). We found that Na-K-Cl cotransport of SHR VSMC is significantly reduced relative to that of WKY VSMC (3.09 vs. 4.39 mumol K.g protein-1.min-1). The apparent ion affinities for Na-K-Cl cotransport of SHR VSMC did not differ from those determined for WKY VSMC. Furthermore, cyclic nucleotide regulation of cotransport also appeared to be the same for the two types of VSMC. In contrast, maximal saturable binding of [3H]bumetanide observed in SHR VSMC was markedly reduced compared with that of WKY VSMC, but the Kd values were similar. Our data suggest that the reduction in cotransport observed in SHR VSMC is the result of a decrease in the number of available cotransport sites.

scholarly journals Cyclic nucleotide signalling compartmentation by PDEs in cultured vascular smooth muscle cells

2019 ◽  
Vol 176 (11) ◽  
pp. 1780-1792 ◽  
Author(s):  
Liang Zhang ◽  
Kaouter Bouadjel ◽  
Boris Manoury ◽  
Grégoire Vandecasteele ◽  
Rodolphe Fischmeister ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Cyclic Nucleotide ◽  
Muscle Cells

scholarly journals Functional expression of smooth muscle-specific ion channels in TGF-β1-treated human adipose-derived mesenchymal stem cells

2013 ◽  
Vol 305 (4) ◽  
pp. C377-C391 ◽  
Author(s):  
Won Sun Park ◽  
Soon Chul Heo ◽  
Eun Su Jeon ◽  
Da Hye Hong ◽  
Youn Kyoung Son ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Ion Channels ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Functional Expression ◽  
Vascular Smcs

Human adipose tissue-derived mesenchymal stem cells (hASCs) have the power to differentiate into various cell types including chondrocytes, osteocytes, adipocytes, neurons, cardiomyocytes, and smooth muscle cells. We characterized the functional expression of ion channels after transforming growth factor-β1 (TGF-β1)-induced differentiation of hASCs, providing insights into the differentiation of vascular smooth muscle cells. The treatment of hASCs with TGF-β1 dramatically increased the contraction of a collagen-gel lattice and the expression levels of specific genes for smooth muscle including α-smooth muscle actin, calponin, smooth mucle-myosin heavy chain, smoothelin-B, myocardin, and h-caldesmon. We observed Ca2+, big-conductance Ca2+-activated K+ (BKCa), and voltage-dependent K+ (Kv) currents in TGF-β1-induced, differentiated hASCs and not in undifferentiated hASCs. The currents share the characteristics of vascular smooth muscle cells (SMCs). RT-PCR and Western blotting revealed that the L-type (Cav1.2) and T-type (Cav3.1, 3.2, and 3.3), known to be expressed in vascular SMCs, dramatically increased along with the Cavβ1 and Cavβ3 subtypes in TGF-β1-induced, differentiated hASCs. Although the expression-level changes of the β-subtype BKCa channels varied, the major α-subtype BKCa channel (KCa1.1) clearly increased in the TGF-β1-induced, differentiated hASCs. Most of the Kv subtypes, also known to be expressed in vascular SMCs, dramatically increased in the TGF-β1-induced, differentiated hASCs. Our results suggest that TGF-β1 induces the increased expression of vascular SMC-like ion channels and the differentiation of hASCs into contractile vascular SMCs.

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