Lycopene binds PDGF-BB and inhibits PDGF-BB-induced intracellular signaling transduction pathway in rat smooth muscle cells

Cardiovascular disease (CVD) is among the leading causes of death worldwide. Micro-RNAs (miRNAs), regulatory molecules that repress protein expression, have attracted considerable attention in CVD research. The vasculature plays a big role in CVD development and progression and dysregulation of vascular cells underlies the root of many vascular diseases. This review provides a brief introduction of the biogenesis of miRNAs and exosomes, followed by overview of the regulatory mechanisms of miRNAs in vascular smooth muscle cells (VSMCs) intracellular signaling during phenotypic switching, senescence, calcification and neointimal hyperplasia. Evidence of extracellular signaling of VSMCs and other cells via exosomal and circulating miRNAs was also presented. Lastly, current drawbacks and limitations of miRNA studies in CVD research and potential ways to overcome these disadvantages were discussed in detail. In-depth understanding of VSMC regulation via miRNAs will add substantial knowledge and advance research in diagnosis, disease progression and/or miRNA-derived therapeutic approaches in CVD research.

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Modulation of smooth muscle contraction by sphingosylphosphorylcholine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.269.3.g370 ◽

1995 ◽

Vol 269 (3) ◽

pp. G370-G377 ◽

Cited By ~ 1

Author(s):

K. N. Bitar ◽

H. Yamada

Keyword(s):

Smooth Muscle ◽

Protein Kinase ◽

Smooth Muscle Cells ◽

Map Kinase ◽

Intracellular Signaling ◽

Calcium Release ◽

Muscle Cells ◽

Smooth Muscle Contraction ◽

Mitogen Activated Protein Kinase ◽

Maximal Response

We have investigated the effect of sphingosylphosphorylcholine (SPC), a synthetic product that was implicated in the sphingomyelin cycle, and have assessed its role in intracellular signaling. SPC induced a dose-dependent contractile effect of smooth muscle cells isolated from the rectosigmoid of the rabbit. Maximal contraction occurred at 10(-6) M. The response started early, 25.4 +/- 6% shortening at 15 s, peaked at 30 s (32.5 +/- 2%), and remained sustained at 8 min (30.0 +/- 3.5%). Preincubation of the cells with thapsigargin had no effect on contraction induced by SPC. The response to a combination of threshold concentrations of inositol 1,4,5-trisphosphate (IP3) and SPC was additive and was significantly different from the maximal response elicited by each agent alone. SPC also induced activation of mitogen-activated protein kinase (MAP kinase). This study demonstrates that SPC is important in cellular signaling of gastrointestinal smooth muscle cells through a mechanism that is independent of IP3-sensitive calcium release and probably through activation of a protein kinase C-mediated activation of MAP kinase.

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Signal transduction pathways of IL-1β-mediated iNOS in pulmonary vascular smooth muscle cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.281.4.l816 ◽

2001 ◽

Vol 281 (4) ◽

pp. L816-L823 ◽

Cited By ~ 14

Author(s):

Jonathan D. Finder ◽

Jennifer L. Petrus ◽

Andrew Hamilton ◽

Raphael T. Villavicencio ◽

Bruce R. Pitt ◽

...

Keyword(s):

Smooth Muscle ◽

Protein Kinase ◽

Pulmonary Artery ◽

Smooth Muscle Cells ◽

Intracellular Signaling ◽

Muscle Cells ◽

Dominant Negative ◽

Janus Kinase ◽

Dominant Negative Mutant ◽

Pulmonary Artery Smooth Muscle

Interleukin (IL)-1β is an important early mediator of inflammation in pulmonary artery smooth muscle cells. We previously reported that a geranylgeranyltransferase inhibitor elevated basal levels of inducible nitric oxide synthase (iNOS) and enhanced IL-1β-mediated induction, suggesting that Rac or Rho small G proteins are candidates for antagonism of such induction. In this study, overexpression of constitutively active Rac1 or its dominant negative mutant did not affect IL-1β induction of iNOS. Alternatively, treatment with Clostridium botulinum C3 exoenzyme, which ADP-ribosylates Rho, was associated with superinduction of iNOS, suggesting an inhibitory role for Rho. IL-1β activated the three mitogen-activated protein kinase (extracellular signal-regulated kinases 1 and 2, c-Jun NH2-terminal kinase/stress-activated protein kinase, and p38) and the Janus kinase (JAK)-signal transducer and activator of transcription pathways. The former two pathways were not associated with IL-1β-mediated iNOS induction, whereas the latter two appeared to have inhibitory roles in iNOS expression. These data suggest that a broad intracellular signaling response to IL-1β in rat pulmonary artery smooth muscle cells results in elevated levels of iNOS that is opposed by the geranylgeranylated small G protein Rho as well as the p38 and JAK2 pathways.

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DIHYDROPYRIDINES INFLUENCE INTRACELLULAR SIGNALING IN VASCULAR SMOOTH MUSCLE CELLS BY INTERFERING DIRECTLY WITH TRANSLOCATION AND MEMBRANE BINDING OF PKC

Journal of Hypertension ◽

10.1097/00004872-200006001-00013 ◽

2000 ◽

Vol 18 ◽

pp. S10

Author(s):

H. Haller ◽

C. Maasch ◽

C. Lindschau ◽

F. C. Luft

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Intracellular Signaling ◽

Membrane Binding ◽

Muscle Cells

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Effects of TH-142177 on angiotensin II-induced proliferation, migration and intracellular signaling in vascular smooth muscle cells and on neointimal thickening after balloon injury

Life Sciences ◽

10.1016/s0024-3205(99)00153-8 ◽

1999 ◽

Vol 64 (22) ◽

pp. 2061-2070 ◽

Cited By ~ 26

Author(s):

Yoshihisa Nozawa ◽

Naosuke Matsuura ◽

Hidekazu Miyake ◽

Shizuo Yamada ◽

Ryohei Kimura

Keyword(s):

Smooth Muscle ◽

Angiotensin Ii ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Intracellular Signaling ◽

Muscle Cells ◽

Balloon Injury ◽

Neointimal Thickening

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NGF Activates Similar Intracellular Signaling Pathways in Vascular Smooth Muscle Cells as PDGF-BB But Elicits Different Biological Responses

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/01.atv.19.4.1041 ◽

1999 ◽

Vol 19 (4) ◽

pp. 1041-1050 ◽

Cited By ~ 46

Author(s):

Rosemary Kraemer ◽

Hiep Nguyen ◽

Keith L. March ◽

Barbara Hempstead

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Signaling Pathways ◽

Vascular Smooth Muscle Cells ◽

Intracellular Signaling ◽

Muscle Cells ◽

Intracellular Signaling Pathways ◽

Biological Responses

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Successful implantation of physiologically functional bioengineered mouse internal anal sphincter

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00269.2009 ◽

2010 ◽

Vol 299 (2) ◽

pp. G430-G439 ◽

Cited By ~ 20

Author(s):

Shreya Raghavan ◽

Eiichi A. Miyasaka ◽

Mohamed Hashish ◽

Sita Somara ◽

Robert R. Gilmont ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Anal Sphincter ◽

Intracellular Signaling ◽

Internal Anal Sphincter ◽

Muscle Cells ◽

Nitric Oxide Donor ◽

Proof Of Concept ◽

Smooth Muscle Tissue ◽

Basal Tone

We have previously developed bioengineered three-dimensional internal anal sphincter (IAS) rings from circular smooth muscle cells isolated from rabbit and human IAS. We provide proof of concept that bioengineered mouse IAS rings are neovascularized upon implantation into mice of the same strain and maintain concentric smooth muscle alignment, phenotype, and IAS functionality. Rings were bioengineered by using smooth muscle cells from the IAS of C57BL/6J mice. Bioengineered mouse IAS rings were implanted subcutaneously on the dorsum of C57BL/6J mice along with a microosmotic pump delivering fibroblast growth factor-2. The mice remained healthy during the period of implantation, showing no external signs of rejection. Mice were killed 28 days postsurgery and implanted IAS rings were harvested. IAS rings showed muscle attachment, neovascularization, healthy color, and no external signs of infection or inflammation. Assessment of force generation on harvested IAS rings showed the following: 1) spontaneous basal tone was generated in the absence of external stimulation; 2) basal tone was relaxed by vasoactive intestinal peptide, nitric oxide donor, and nifedipine; 3) acetylcholine and phorbol dibutyrate elicited rapid-rising, dose-dependent, sustained contractions repeatedly over 30 min without signs of muscle fatigue; and 4) magnitudes of potassium chloride-induced contractions were 100% of peak maximal agonist-induced contractions. Our preliminary results confirm the proof of concept that bioengineered rings are neovascularized upon implantation. Harvested rings maintain smooth muscle alignment and phenotype. Our physiological studies confirm that implanted rings maintain 1) overall IAS physiology and develop basal tone, 2) integrity of membrane ionic characteristics, and 3) integrity of membrane associated intracellular signaling transduction pathways for contraction and relaxation by responding to cholinergic, nitrergic, and VIP-ergic stimulation. IAS smooth muscle tissue could thus be bioengineered for the purpose of implantation to serve as a potential graft therapy for dysfunctional internal anal sphincter in fecal incontinence.

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