Objective-Myocardin is a coactivator of serum response factor (SRF) required for vascular smooth muscle cell (VSMC) differentiation. HERP1 is a transcriptional repressor, which is abundantly expressed in vascular system and is known to function as a target gene of Notch. However, the role of HERP1 in the pathogenesis of vascular lesions remains unknown. The present study characterizes the expression of HERP1 in normal and diseased vessels, and tests the hypothesis that HERP1 inhibits SRF/myocardin-dependent SMC gene expression. Methods and Results-Immunohistochemistry revealed that HERP1 and myocardin expression was localized to SMC in the neointima of balloon-injured rat aorta and in human coronary atherosclerotic lesions. Expression of both HERP1 and myocardin was elevated in cultured VSMCs compared with medial SMC. Overexpressed HERP1 inhibited the myocardin-induced SMC marker gene expression in 10T1/2 cells. HERP1 protein interfered with the SRF/CArG-box interaction in vivo and in vitro. Immunoprecipitation assays showed that HERP1 physically interacts with SRF. Conclusions-HERP1 expression was associated with the SMC proliferation and dedifferentiation in vitro and in vivo.HERP1 may play a role in promoting the phenotypic modulation of VSMCs during vascular injury and atherosclerotic process by interfering with SRF binding to CArG-box through physical association between HERP1 and SRF. Key Words: HERP1 Ⅲ myocardin Ⅲ serum response factor Ⅲ smooth muscle cells P henotypic modulation of vascular smooth muscle cells (VSMCs) from contractile to synthetic forms plays a pivotal role in the pathogenesis of vascular diseases including atherosclerosis and restenosis after angioplasty. 1 It is wellestablished that VSMC phenotype is regulated by a complex array of local environmental cues including humoral factors, cell-cell and cell-matrix interactions, inflammatory stimuli, and mechanical stresses. Such complex stimuli downregulate a number of genes required for the contractile phenotype in synthetic VSMCs. These include smooth muscle myosin heavy chain (SM-MHC), SM22␣, caldesmon, and calponin. Because the genes encoding these proteins are differentially expressed depending on the proliferative state of VSMCs, transcription factors regulated by numerous stimuli are responsible at least in part for the distinct pattern of gene expression seen in synthetic VSMCs.There is mounting evidence that most SMC marker proteins such as SM-MHC and SM22␣ are controlled by serum response factor (SRF), which binds to a sequence known as a CArG box and recruits a potent coactivator, myocardin, for SMC differentiation. 1 When myocardin is ectopically expressed in nonmuscle cells, it can induce SMC differentiation. 2,3 Most importantly, mouse embryos deficient for myocardin show no evidence of vascular SMC, indicating myocardin as a necessary and sufficient factor for SMC differentiation in vivo. 4 These observations, in conjunction with downregulation of SMC marker genes in synthetic VSMC, led us to speculate that myocardin express...

INTRODUCTIONRecent studies have shown that the eradication of Helicobacter pylori leads to normalized gastric acid secretion 1±3 and prevents ulcer recurrence in patients with peptic ulcer diseases. 4,5 Now, the focus is on whether the eradication of H. pylori reverses the decrease in gastric acid secretion seen in patients with chronic gastritis, because hypo-or achlorhydria is known to be an important risk factor for the development of gastric cancer.6±8 Several recent studies have shown an increase in gastric acid secretion in H. pyloripositive subjects after H. pylori eradication therapy, 9±13although the mechanism responsible for this change remains unclear.In this study we evaluated the effect of H. pylori eradication on 24-h acidity in patients with moderate or severe atrophic gastritis of the corpus. In addition, we investigated whether atrophy was reversible after the eradication of H. pylori. SUBJECTS AND METHODS SubjectsSixteen H. pylori-positive patients with histologically proven moderate or severe atrophic gastritis of the corpus were enrolled in a pre-and post-therapy design SUMMARY Background: Recent studies have shown that the eradication of Helicobacter pylori results in a gastric acid secretion which decreases to normal levels in patients with duodenal ulcer disease. Aim: To evaluate the effect of eradication of H. pylori in a 24-h study of gastric acidity in patients with atrophic gastritis of the corpus. Methods: Intragastric acidity was measured by continuous 24-h pH monitoring, and the histology of the gastric antrum and corpus were evaluated in 14 H. pyloripositive patients with histologically proven atrophic gastritis of the corpus (10 men, four women; mean age, 57 years) before and 1 year after anti-H. pylori therapy.

In functional dyspepsia patients, delayed gastric emptying of a solid meal was related to antral hypomotility during the early postprandial phase. Ultrasonographic assessment of gastric motility in both liquid and solid meals may provide a better understanding of the pathogenesis of functional dyspepsia.

These studies suggest that the adventitia may play a role in vascular lesion formation after balloon overstretch injury of pig coronary arteries by contributing to the cellular mass of the neointima and the synthesis of growth factors. In addition, the adventitia may contribute to vascular remodeling and constriction of the external elastic lamina through accumulation of myofibroblasts containing alpha smooth muscle actin in the adventitia surrounding the injury site. Inhibition of myofibroblast proliferation and/or recruitment by intravascular brachytherapy positively affects vascular remodeling through its action on adventitial cells. Inflammation is a major event associated with balloon angioplasty, resulting in the sequential recruitment of neutrophils (2‐24 hours) and monocyte/macrophages (24‐72 hours) predominantly into the adventitia surrounding the injury site. It is hypothesized that inflammatory cells release cytokines and/or increase the production of superoxides which stimulate the proliferation and recruitment of adventitial myofibroblasts. Inflammatory and proliferative responses were not confined to the local adventitia but were found extending as far as 1‐3 mm away from the injured vessel in the distal perivascular tissues. Studies were performed to examine the expression of genes associated with cell migration at early times after injury in an attempt to determine the source of the adventitial myofibroblasts. Expression of genes involved in cell migration including MMP‐2, MMP‐9, and tenascin was found as early as 2 hours following angioplasty in the intramyocardial, pericardial, and adipose tissue fibroblasts. While these studies suggest that local tissue was the source of the myofibroblasts recruited to the injury site, we have been unable to confirm this finding by direct fluorescent labeling of adventitial cells. Recent work from our laboratory suggests that myofibroblast precursors may be isolated from buffy coat preparations from peripheral blood. These results lead us to hypothesize that stem cells that differentiate into myofibroblasts may be recruited in early inflammatory infiltrates in the adventitia. Clearly, additional work will have to be directed at a more detailed examination of the response of adventitial and other perivascular cells and tissues to balloon injury to determine their sources and their role in regulating vascular lesion development.