Mueller polarimetric imaging for fast macroscopic mapping of microscopic collagen matrix remodeling by smooth muscle cells

AbstractSmooth muscle cells (SMCs) are critical players in cardiovascular disease development and undergo complex phenotype switching during disease progression. However, SMC phenotype is difficult to assess and track in co-culture studies. To determine the contractility of SMCs embedded within collagen hydrogels, we performed polarized light imaging and subsequent analysis based on Mueller matrices. Measurements were made both in the absence and presence of endothelial cells (ECs) in order to establish the impact of EC-SMC communication on SMC contractility. The results demonstrated that Mueller polarimetric imaging is indeed an appropriate tool for assessing SMC activity which significantly modifies the hydrogel retardance in the presence of ECs. These findings are consistent with the idea that EC-SMC communication promotes a more contractile SMC phenotype. More broadly, our findings suggest that Mueller polarimetry can be a useful tool for studies of spatial heterogeneities in hydrogel remodeling by SMCs.

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Abstract 477: Diverse Actions of the EP4 Prostaglandin E2 Receptor in Blood Pressure Control

Hypertension ◽

10.1161/hyp.62.suppl_1.a477 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Marcela Herrera ◽

Matthew A Sparks ◽

Beverky H Koller ◽

Thomas M Coffman

Keyword(s):

Smooth Muscle ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Smooth Muscle Cells ◽

Prostaglandin E2 ◽

Ductus Arteriosus ◽

Muscle Cells ◽

High Salt ◽

Ang Ii ◽

The Impact

Prostaglandin E2 (PGE2) is a major prostanoid produced by the kidney having the potential to influence renal blood flow, Na excretion, and thus mean arterial pressure (BP). PGE2 actions are mediated by four distinct E-prostanoid (EP) receptor isoforms: EP1-EP4. The EP4 receptor (EP4R) triggers macula densa stimulation of renin, induces vasodilation, and may inhibit epithelial sodium transport. Thus, the impact of EP4Rs on BP may differ with the sites of PGE2 synthesis and pattern of EP4R activation within the kidney. To examine the role of EP4R on BP regulation we generated EP4R-deficient mice. Because deletion of EP4R in utero causes peri-natal mortality due to persistent patent ductus arteriosus, we carried out conditional deletion by crossing EP4flox/flox with a transgenic line with tamoxifen-inducible Cre expression in all tissues. Resting mean arterial pressure (MAP) measured by radiotelemetry was increased by 5±1mm Hg (p<0.05) in mice with total-body EP4R-deficiency (EP4R-TBKO) vs. controls. In addition, EP4R-TBKOs had an exaggerated increase in MAP with high-salt (6% NaCl) feeding (MAP increase: 5±1 vs. 2±1mmHg for controls; p<0.05) and during angiotensin II (Ang II)-dependent hypertension (MAP increase: 37±2 vs. 24±3mmHg for controls; p<0.05). We next hypothesized that exaggerated hypertension in the EP4R-TBKOs was due to elimination of compensatory EP4R-depedent vasodilation mediated by direct actions in vascular smooth muscle cells (VSMCs). Accordingly, we generated mice lacking EP4R in VSMCs (EP4R-SMKOs) using EP4flox/flox and transgenic mice with tamoxifen-inducible expression of Cre limited to smooth muscle cells. In contrast to the EP4R-TBKOs, elimination of EP4R only from VSMC reduced resting MAP by 5±1mm Hg (p<0.04) but did not affect the BP response to high salt feeding (MAP change: 2±1 vs. 2±1 mm Hg; ns) or chronic Ang II infusion (MAP increase: 29±3 vs. 34±4 mm Hg; ns). Thus, the EP4R modulates resting MAP but its specific impact may vary between EP4R populations in different cell lineages. EP4Rs resist the development of salt- and Ang II-dependent hypertension. These anti-hypertensive actions are not mediated by direct effects of EP4R in VSMCs, but may involve EP4R in endothelium, brain, or kidney epithelia.

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Erratum to Decomposition cross-correlation for analysis of collagen matrix deformation by single smooth muscle cells

Medical & Biological Engineering & Computing ◽

10.1007/s11517-008-0337-8 ◽

2008 ◽

Vol 46 (5) ◽

pp. 517-517

Author(s):

Jeroen van den Akker ◽

Adrian Pistea ◽

Erik N. T. P. Bakker ◽

Ed VanBavel

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Cross Correlation ◽

Collagen Matrix ◽

Muscle Cells ◽

Matrix Deformation

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Pulmonary artery smooth muscle cells from normal subjects and IPAH patients show divergent cAMP-mediated effects on TRPC expression and capacitative Ca2+ entry

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00214.2006 ◽

2007 ◽

Vol 292 (5) ◽

pp. L1202-L1210 ◽

Cited By ~ 70

Author(s):

Shen Zhang ◽

Hemal H. Patel ◽

Fiona Murray ◽

Carmelle V. Remillard ◽

Christian Schach ◽

...

Keyword(s):

Smooth Muscle ◽

Pulmonary Artery ◽

Smooth Muscle Cells ◽

Transient Receptor Potential ◽

Phosphodiesterase Inhibitor ◽

Receptor Potential ◽

Muscle Cells ◽

Normal Subjects ◽

Pulmonary Artery Smooth Muscle ◽

The Impact

Pulmonary vascular remodeling due to overgrowth of pulmonary artery smooth muscle cells (PASMC) is a major cause for the elevated vascular resistance in patients with idiopathic pulmonary arterial hypertension (IPAH). Increased cytosolic Ca2+ concentration, resulting from enhanced capacitative Ca2+ entry (CCE) and upregulated transient receptor potential (TRP) channel expression, is involved in stimulating PASMC proliferation. The current study was designed to determine the impact of cAMP, a second messenger that we hypothesized would blunt aspects of PASMC activity, as a possible contributor to IPAH pathophysiology. Short-term (30 min) pretreatment with forskolin (FSK; 10 μM), a direct activator of adenylyl cyclase, in combination with the cyclic nucleotide phosphodiesterase inhibitor isobutylmethylxanthine (IBMX; 200 μM), attenuated CCE in PASMC from normal subjects, patients without pulmonary hypertension (NPH), and patients with IPAH. The FSK-mediated CCE inhibition was independent of protein kinase A (PKA), because the PKA inhibitor H89 negligibly affected the decrease in CCE produced by cAMP. By contrast, longer (4 h) treatment with FSK (with IBMX) attenuated CCE in normal and NPH PASMC but enhanced CCE in IPAH PASMC. This enhancement of CCE was abolished by PKA inhibition and associated with an upregulation of TRPC3. In addition, cAMP increased TRPC1 mRNA expression in IPAH (but not in normal or NPH) PASMC, an effect blunted by H89. Furthermore, iloprost, a prostacyclin analog that increases cAMP, downregulated TRPC3 expression in IPAH PASMC and FSK-mediated cAMP increase inhibited IPAH PASMC proliferation. Although a rapid rise in cellular cAMP decreases CCE by a PKA-independent mechanism, sustained cAMP increase inhibits CCE in normal and NPH PASMC but increases CCE via a PKA-dependent pathway in IPAH PASMC. The divergent effect of cAMP on CCE parallels effects on TRPC expression. The results suggest that the combined use of a PKA inhibitor and cAMP-elevating drugs may provide a novel approach for treatment of IPAH.

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Regulation of contractile signaling and matrix remodeling by T-cadherin in vascular smooth muscle cells: Constitutive and insulin-dependent effects

Cellular Signalling ◽

10.1016/j.cellsig.2014.05.001 ◽

2014 ◽

Vol 26 (9) ◽

pp. 1897-1908 ◽

Cited By ~ 11

Author(s):

Agne Frismantiene ◽

Dennis Pfaff ◽

Audrey Frachet ◽

Matteo Coen ◽

Manjunath B. Joshi ◽

...

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Matrix Remodeling ◽

Insulin Dependent

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Tetraspanin CD9 Is Associated With Very Late–Acting Integrins in Human Vascular Smooth Muscle Cells and Modulates Collagen Matrix Reorganization

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/01.atv.18.11.1691 ◽

1998 ◽

Vol 18 (11) ◽

pp. 1691-1697 ◽

Cited By ~ 21

Author(s):

Arnaud Scherberich ◽

Sylvie Moog ◽

Gisèle Haan-Archipoff ◽

David O. Azorsa ◽

François Lanza ◽

...

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Collagen Matrix ◽

Muscle Cells

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The Modulatory Effect of Ischemia and Reperfusion on Arginine Vasopressin-Induced Arterial Reactions

BioMed Research International ◽

10.1155/2016/3679048 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Katarzyna Szadujkis-Szadurska ◽

Bartosz Malinowski ◽

Małgorzata Piotrowska ◽

Grzegorz Grześk ◽

Michał Wiciński ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Arginine Vasopressin ◽

Muscle Cells ◽

Signalling Pathway ◽

Ischemia And Reperfusion ◽

Dependent Manner ◽

Male Wistar Rats ◽

The Impact

Aim of the Study.The purpose of this study was to investigate the impact of ischemia and reperfusion on the resistance of arteries to AVP (arginine vasopressin), with a particular emphasis on the role of smooth muscle cells in the action of vasopressin receptors and the role of the cGMP-associated signalling pathway.Materials and Methods.Experiment was performed on the perfunded tail arteries from male Wistar rats. The constriction triggered by AVP after 30 minutes of ischemia and 30 and 90 minutes of reperfusion was analysed. Analogous experiments were also carried out in the presence of 8Br-cGMP.Results.Ischemia reduces and reperfusion increases in a time-dependent manner the arterial reaction to AVP. The presence of 8Br-cGMP causes a significant decrease of arterial reactivity under study conditions.Conclusions.Ischemia and reperfusion modulate arterial contraction triggered by AVP. The effect of 8Br-cGMP on reactions, induced by AVP after ischemia and reperfusion, indicates that signalling pathway associated with nitric oxide (NO) and cGMP regulates the tension of the vascular smooth muscle cells.

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miR-200c is aberrantly expressed in leiomyomas in an ethnic-dependent manner and targets ZEBs, VEGFA, TIMP2, and FBLN5

Endocrine Related Cancer ◽

10.1530/erc-12-0007 ◽

2012 ◽

Vol 19 (4) ◽

pp. 541-556 ◽

Cited By ~ 46

Author(s):

Tsai-Der Chuang ◽

Harekrushna Panda ◽

Xiaoping Luo ◽

Nasser Chegini

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Target Genes ◽

Abnormal Uterine Bleeding ◽

Muscle Cells ◽

Matrix Remodeling ◽

Dependent Manner ◽

Vimentin Expression ◽

Altered Expression ◽

Uterine Tumors

MicroRNA-200c (miR-200c) through repression of specific target genes has been associated with cellular transition, tumorigenesis, and tissue fibrosis. We explored the expression and functional aspects of miR-200c in genesis of leiomyomas (LYO), benign uterine tumors with fibrotic characteristic. Using LYO and matched myometrium (MYO;n=76) from untreated and from patients exposed to hormonal therapies (GNRH agonist (GNRHa), Depo-Provera, and oral contraceptives), we found that miR-200c was expressed at significantly lower levels (P<0.05) in LYO as compared with MYO. These levels were lower in LYO from African Americans as compared with Caucasians, patients experiencing abnormal uterine bleeding and those exposed to GNRHa therapy. Gain-of-function of miR-200c in isolated leiomyoma smooth muscle cells (LSMCs), myometrial smooth muscle cells (MSMCs), and leiomyosarcoma cell line (SKLM-S1) repressedZEB1/ZEB2mRNAs and proteins, with concurrent increase in E-cadherin (CDH1) and reduction in vimentin expression, phenotypic alteration, and inhibition of MSMC and LSMC proliferations. We further validatedTIMP2, FBLN5, andVEGFAas direct targets of miR-200c through interaction with their respective 3′ UTRs, and other genes as determined by microarray analysis. At tissue levels, LYO expressed lower levels ofTIMP2andFBLN5mRNAs but increased protein expressions, which to some extent altered due to hormonal exposure. Given the regulatory functions ofZEBs, VEGFA, FBLN5, andTIMP2on cellular activities that promote cellular transition, angiogenesis, and matrix remodeling, we concluded that altered expression of miR-200c may have a significant impact on the outcome of LYO growth, maintenance of their mesenchymal and fibrotic characteristics, and possibly their associated symptoms.

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Stem Cells and Vascular Regenerative Medicine

ASME 2008 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2008-193591 ◽

2008 ◽

Author(s):

Taby Ahsan ◽

Adele M. Doyle ◽

Garry P. Duffy ◽

Frank Barry ◽

Robert M. Nerem

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Smooth Muscle ◽

Regenerative Medicine ◽

Blood Vessel ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

In Vitro Proliferation ◽

The Impact ◽

Blood Vessel Substitutes

Vascular applications in regenerative medicine include blood vessel substitutes and vasculogenesis in ischemic or engineered tissues. For these repair processes to be successful, there is a need for a stable supply of endothelial and smooth muscle cells. For blood vessel substitutes, the immediate goal is to enable blood flow, but vasoactivity is necessary for long term success. In engineered vessels, it is thought that endothelial cells will serve as an anti-thrombogenic lumenal layer, while smooth muscle cells contribute to vessel contractility. In other clinical applications, what is needed is not a vessel substitute but the promotion of new vessel formation (vasculogenesis). A simplified account of vasculogenesis is that endothelial cells assemble to form vessel-like structures that can then be stabilized by smooth muscle cells. Overall, the need for new vasculature to transfer oxygen and nutrients is important to reperfuse not only ischemic tissue in vivo, but also dense, structurally complex engineered tissue. The impact of these vascular therapies, however, is limited in part by the low yield and inadequate in vitro proliferation potential of primary endothelial and smooth muscle cells. Thus, there is a need to address the cell sourcing issue for vascular cell-based therapies, potentially using stem cells.

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Cytoglobin overexpression facilitates proliferation and migration of vascular smooth muscle cells

Archives of Biological Sciences ◽

10.2298/abs191024009l ◽

2020 ◽

Vol 72 (2) ◽

pp. 165-172 ◽

Cited By ~ 1

Author(s):

Lei Li ◽

Yilin Xie ◽

Shen Li ◽

Juanjuan Tan ◽

Yingchun Qin ◽

...

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Feedback Regulation ◽

Muscle Cells ◽

Nuclear Antigen ◽

Matrix Remodeling ◽

Negative Feedback Regulation ◽

Vsmc Proliferation

Cytoglobin, a recently discovered globin, is expressed in vascular smooth muscle cells (VSMCs). Loss of cytoglobin provides a protective effect on vascular reconstruction but the effect of its overexpression is unclear. The aim of the study was to investigate the effect of cytoglobin overexpression on the migration and proliferation of VSMCs and possible mechanisms. We detected the expression of cytoglobin in hypertensive and normotensive rat aortas, with negative feedback regulation between cytoglobin and hypertension observed. The expression of cytoglobin was significantly decreased in hypertensive rats compared to normotensive rats, but VSMCs overexpressing cytoglobin displayed increased cell migration and proliferation, which led to a phenotypic switch. The increased expression of matrix metalloproteinase 9 and collagen Ia suggests a role for cytoglobin in extracellular matrix remodeling. Increased expression of proliferating cell nuclear antigen and decreased expression of p27 implies that cytoglobin is involved in modulating VSMC proliferation. Our findings indicate that cytoglobin may play an important role in vascular wall remodeling.

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