The small heat shock-related protein 20 (HSP20) is present in four isoforms in bovine carotid artery smooth muscles. Three of the isoforms are phosphorylated and one is not. Increases in the phosphorylation of two isoforms of HSP20 (isoform 3, pI 5.9; and 8, pI 5.7) are associated with cyclic nucleotide-dependent relaxation of bovine carotid artery smooth muscles. Increases in the phosphorylation of another isoform (isoform 4, pI 6.0) are associated with phorbol ester-induced contraction of bovine carotid artery smooth muscles. In this investigation we determined that isoforms 3 and 8 are phosphorylated on Ser 16 of the HSP20 molecule during activation of cAMP-dependent signaling pathways. Phosphorylation state-specific antibodies produced against a peptide containing phosphorylated Ser 16 recognized isoforms 3 and 8 but not isoform 4. In human vascular tissue, only isoform 3 is present. Incubation of transiently permeabilized strips of bovine carotid artery smooth muscle with synthetic peptides in which Ser 16 is phosphorylated, inhibits contractile responses to high extracellular KCl and to serotonin. These data suggest that phosphorylation of HSP20 on Ser 16 modulates cAMP-dependent vasorelaxation.A major phosphorylation event that occurs with cyclic nucleotide-dependent relaxation of vascular smooth muscle is an increase in the phosphorylation of two 20-kDa proteins (isoform 3, pI 5.9; and 8, pI 5.7) (1-3). We recently identified these 20-kDa phosphoproteins as different phosphorylated forms of a small heat shock-related protein, HSP20 1 (4). In addition, HSP20 can be phosphorylated in vitro by both cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) (4). HSP20 is also phosphorylated during endothelialdependent vasorelaxation of isolated segments of bovine carotid artery smooth muscle (5).In a vascular smooth muscle, umbilical artery smooth muscle, that is refractory to cyclic nucleotide-dependent vasorelaxation, there is no significant increase in the phosphorylation of HSP20 in response to activation of PKA or PKG (2). HSP20 is present in umbilical artery smooth muscle and can be phosphorylated by PKA in vitro using homogenates of umbilical smooth muscle (6). Taken together, these data support a role for phosphorylated HSP20 in mediating cyclic nucleotide-dependent vasorelaxation.Histamine and phorbol ester-induced contractions of bovine carotid artery smooth muscle are associated with an increase in the phosphorylation of another 20-kDa protein (isoform 4, pI 6.0) (1). The subsequent activation of cyclic nucleotide-dependent signaling pathways leads to a decrease in the phosphorylation of isoform 4. This 20-kDa protein is immunoreactive with specific polyclonal antibodies raised against HSP20 (4). Thus, increases in the phosphorylation of this isoform of HSP20 are associated with smooth muscle contraction and decreases are associated with activation of cyclic nucleotide-dependent signaling pathways.The purpose of this investigation was to determine the specific site on the HSP20 mo...

These results confirm our hypothesis that the source of cells resulting in venous stenosis formation is derived from the adventitia and media, with cell migration being greatest within the first two weeks after graft placement with translocation of these cells into the intima at four weeks. MMP-2 activity peaks at day seven in the adventitia and again at days 19 to 26 in the intima. A key to limiting venous stenosis formation may lie in inhibiting MMP-2 by adventitial and medial targeting.

Cryoablation is a safe and effective treatment for pulmonary metastases with preserved quality of life following intervention.

Purpose To assess 12-month outcomes and safety of clinical magnetic resonance (MR)–guided focused ultrasound (US) treatments of uterine leiomyomas. Materials and Methods Between March 2005 and December 2009, 150 women with symptomatic uterine leiomyomas were clinically treated with MR-guided focused US at a single institution; 130 patients completed treatment and agreed to have their data used for research purposes. Patients were followed through retrospective review of medical records and phone interviews conducted at 3-, 6-, and 12-month intervals after treatment to assess additional procedures and symptom relief. Outcome measures and treatment complications were analyzed for possible correlations with the appearance of the tumors on T2-weighted imaging. Results The cumulative incidence of additional tumor-related treatments 12 months after MR-guided focused US was 7.4% by the Kaplan–Meier method. At 3-, 6-, and 12-month follow-up, 86% (90 of 105), 93% (92 of 99), and 88% (78 of 89) of patients reported relief of symptoms, respectively. No statistically significant correlation between tumor appearance on T2-weighted imaging and 12-month outcome was found. Treatment-related complications were observed in 17 patients (13.1%): 16 patients had minor complications and one had a major complication (deep vein thrombosis). All complications were resolved within the 12-month follow-up period. Conclusions MR-guided focused US is a noninvasive treatment option that can be used to effectively and safely treat uterine leiomyomas and delivers significant and lasting symptom relief for at least 12 months. The incidence of additional treatment during this time period is comparable with those in previous reports of uterine artery embolization.

Purpose The purpose of this study is to demonstrate feasibility of using magnetic resonance elastography (MRE) to identify hypertensive changes in the abdominal aorta when compared to normotensives based on the stiffness measurements. Methods MRE was performed on 8 volunteers (4 normotensives and 4 hypertensives) to measure the effective stiffness of the abdominal aorta. MRE wave images are directionally filtered and phase gradient analysis was performed to determine the stiffness of the aorta. Student’s t-test was performed to determine significant difference in stiffness measurements between normotensives and hypertensives. Results The normotensive group demonstrated an average abdominal aortic stiffness of 3.7 ± 0.8 kPa, while the controlled-hypertensive demonstrated an average abdominal aortic stiffness of 9.3 ± 1.9kPa. MRE effective stiffness of abdominal aorta in hypertensives was significantly greater than that of normotensives with p=0.02. Conclusion Feasibility of in vivo aortic MRE is demonstrated. Hypertensives have significantly higher aortic stiffness assessed through MRE than normotensives.

Cyclic nucleotide-dependent vasorelaxation is associated with increases in the phosphorylation of a small heat shock-related protein, HSP20. We hypothesized that phosphorylation of HSP20 in vascular smooth muscles is associated with alterations in the macromolecular associations of HSP20. Treatment of bovine carotid artery smooth muscles with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and the adenylate cyclase activator, forskolin, led to increases in the phosphorylation of HSP20 and dissociation of macromolecular aggregates of HSP20. However, 3-isobutyl-1-methylxanthine and forskolin treatment of a muscle that is uniquely refractory to cyclic nucleotide-dependent vasorelaxation, human umbilical artery smooth muscle, did not result in increases in the phosphorylation of HSP20 or to dissociation of macromolecular aggregates. HSP20 can be phosphorylated in vitro by the catalytic subunit of cAMP-dependent protein kinase (PKA) in both carotid and umbilical arteries and this phosphorylation of HSP20 is associated with dissociation of macromolecular aggregates of HSP20. Activation of cyclic nucleotide-dependent signaling pathways does not lead to changes in the macromolecular associations of another small heat shock protein, HSP27. Interestingly, the myosin light chains (MLC 20 ) are in similar fractions as the HSP20, and phosphorylation of HSP20 is associated with changes in the macromolecular associations of MLC 20 . These data suggest that increases in the phosphorylation of HSP20 are associated with changes in the macromolecular associations of HSP20. HSP20 may regulate vasorelaxation through a direct interaction with specific contractile regulatory proteins.Agonist pre-contracted bovine carotid artery smooth muscle relaxes with the addition of the guanylyl cyclase activator, sodium nitroprusside, or the adenylyl cyclase activator, forskolin. This relaxation is associated with increases in the phosphorylation of the small heat shock-related protein, HSP20 1 (1). In addition, endothelial-dependent vasodilation of isolated segments of bovine carotid arteries is also associated with increases in the phosphorylation of HSP20 (2). However, HSP20 is not phosphorylated in a muscle that is uniquely refractory to cyclic nucleotide-dependent relaxation, human umbilical artery smooth muscle (3,4). These data suggest that increases in the phosphorylation of HSP20 may mediate cellular signaling processes that lead to vasorelaxation. HSP20 was initially identified as a by-product of the purification of another small heat shock protein, HSP27 (5). HSP27 has been shown to modulate actin filament dynamics in cultured cells (7-9). Increases in the phosphorylation of HSP27 have been associated with vascular smooth muscle contraction (10 -12). HSP20 has been shown to associate in macromolecular aggregates with HSP27, in extracts from heart, diaphragm, and soleus muscle cells (5). Both HSP20 and HSP27 dissociate from the aggregated form in response to heat stress (5, 6). HSP20 and HSP27 are predominant proteins in ...

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Uterine fibroids are common smooth muscle tumors, which can result in substantial symptoms affecting the quality of life of women. Whereas patients have several options available for treatment, focused ultrasound ablation is one of the least invasive treatment options outside medical therapy. Magnetic resonance-guided focused ultrasound (MRgFUS) ablation combines therapy delivered by an ultrasound transducer with imaging, guidance for therapy, and thermal feedback provided by magnetic resonance imaging. In 2004, the MRgFUS system ExAblate 2000 (InSightec, Haifa, Israel) was approved by the United States Food and Drug Administration for clinical treatments of uterine fibroids. Since its approval, our institution has performed more than 140 treatments. This paper provides an overview of our site's clinical experience with MRgFUS, including a brief description of the treatment system, pertinent features to review on screening magnetic resonance imaging, how the procedure is performed, and risks and benefits of the treatment. Some potential clinical applications of the technology are also briefly reviewed.