摘要:

Inflammatory diseases may have a role in the pathogenesis of atherosclerosis. Several epidemiological and clinical studies have explored the possible association betweenHelicobacter pyloriseropositivity, cardiovascular risk factors, and ischemic heart disease. The contradictory results of these studies have fueled a debate regarding the link betweenH pyloriinfection and atherogenesis. This study tested the hypothesis thatH pyloriinfection might influence atherosclerosis in vivo in mice. Male wild-type C57/Bl6 mice and LDL-receptor deficient congenic mice were randomly assigned for infection withH pylori. All animals were fed a high-cholesterol diet (1.25%) for 6 or 12 weeks. At autopsy, we compared aortic atherosclerotic lesion formation and lipid deposition.H pyloriinfection influenced neither the progression of atherosclerotic lesions nor lipid deposition. Moreover, the cellularity of atherosclerotic lesions (macrophages and T cells) did not differ between mice infected or not infected withH pylori. This in vivo study performed in a mouse model of atherosclerosis revealed no indication thatH pyloriinfection might contribute to the development of atherosclerotic lesion formation. The full text of this article is available at http://www.circresaha.org.

ISSN:0009-7330    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Fibroblast growth factor 2 (FGF2) signaling is involved in angiogenesis, vascular contractility, and cardiac hypertrophy. Mice lacking a functionalFGF2gene (FGF2−/−) are hypotensive, but the primary physiological role of FGF2 in cardiovascular homeostasis remained unknown. Using a chickenFGF2(cFGF2) transgene under control of theWnt-1promotor, we selectively re-expressed FGF2 in the developing nervous system of FGF2−/−(transgenic FGF2 mutant) embryos. Expression of thecFGF2transgene in the developing nervous system, including its autonomic region, was limited to the period between embryonic day 9.5 and 14.5. Significantly, noFGF2re-expression was detected in developing heart and blood vessels. Pharmacological analysis revealed a normalization of the blood pressure response to isoproterenol-induced vasodilation in adult transgenic FGF2 mutant mice. In addition, the hypotensive phenotype was rescued in 1 line (of 2) transgenic FGF2 mutant adult mice having expressed higher levels of cFGF2 proteins during nervous system development. These genetic studies indicate that FGF2 signaling is essential for complete development of the neural circuitry required for central regulation of blood pressure, whereas it appears dispensable for blood pressure control in the healthy adult. The full text of this article is available at http://www.circresaha.org.

ISSN:0009-7330    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Brugada syndrome is an inherited cardiac disorder caused by mutations in the cardiac sodium channel gene,SCN5A,that leads to ventricular fibrillation and sudden death. This study reports the changes in functional expression and cellular localization of anSCN5Adouble mutant (R1232W/T1620M) recently discovered in patients with Brugada syndrome. Mutant and wild-type (WT) human heart sodium channels (hNav1.5) were expressed in tsA201 cells in the presence of the &bgr;1-auxiliary subunit. Patch-clamp experiments in whole-cell configuration were conducted to assess functional expression. Immunohistochemistry and confocal microscopy were used to determine the spatial distribution of either WT or mutant cardiac sodium channels. The results show an abolition of functional sodium channel expression of the hNav1.5/R1232W/T1620M mutant in the tsA201 cells. A conservative positively charged mutant, hNav1.5/R1232K/T1620M, produced functional channels. Immunofluorescent staining showed that the FLAG-tagged hNav1.5/WT transfected into tsA201 cells was localized on the cell surface, whereas the FLAG-tagged hNav1.5/R1232W/T1620M mutant was colocalized with calnexin within the endoplasmic reticulum (ER). These results indicate that a positively charged arginine or lysine residue at position 1232 in the double mutant is required for the proper transport and functional expression of the hNav1.5 protein. These results support the concept that loss of function of the cardiac Na+channel is responsible for the Brugada syndrome. The full text of this article is available at http://www.circresaha.org.

ISSN:0009-7330    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

To study the role of cGMP-dependent protein kinase I (cGKI) for cardiac contractility, force of contraction (Fc) was studied in electrically driven heart muscle from wild-type (WT) mice and from conventional and conditional cGKI knockout mice. Both 8-Br-cGMP and 8-pCPT-cGMP reduced Fc in cardiac muscle from juvenile WT but not from juvenile cGKI-null mutants. Similarly, the cGMP analogues reduced Fcin forskolin-stimulated ventricular muscle from WT mice but not from cGKI-null mutants. In contrast, carbachol reduced Fcin both groups of animals. 8-Br-cGMP reduced Fcalso in heart muscle from adult WT mice but not from adult cardiomyocyte-specific cGKI-knockout mice. These results demonstrate that cGKI mediates the negative inotropic effect of cGMP in the myocardium of juvenile and adult mice.

ISSN:0009-7330    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Nitric oxide (NO) mediates multiple physiological and pathophysiological processes in the cardiovascular system. Pharmacological compounds that release NO have been useful tools for evaluating the pivotal role of NO in cardiovascular physiology and therapeutics. These agents constitute two broad classes of compounds, those that release NO or one of its redox congeners spontaneously and those that require enzymatic metabolism to generate NO. In addition, several commonly used cardiovascular drugs exert their beneficial action, in part, by modulating the NO pathway. Here, we review these classes of agents, summarizing their fundamental chemistry and pharmacology, and provide an overview of their cardiovascular mechanisms of action.

ISSN:0009-7330    

出版商:OVID    

年代:2002

数据来源: OVID