Expression and localization of renin and angiotensinogen in rat heart after myocardial infarction

Wistar-Kyoto rats underwent myocardial infarction (MI) or sham surgery. At different time points after surgery (1-90 days), hearts were removed and divided into infarcted left ventricle (LV), noninfarcted septum, and right ventricle. The tissues were used for total RNA isolation or Formalin fixation for in situ hybridization (ISH). Renin and angiotensinogen mRNA contents were quantified by the competitive reverse transcriptase polymerase chain reaction. We found a 4-, 14-, and 8-fold increase (P <0.05, n = 6) in renin mRNA in the infarcted LV at 2, 4, and 7 days after MI, respectively. No differences were observed between angiotensinogen mRNA levels in sham and infarcted hearts. ISH at 4 days after surgery revealed a dense renin mRNA labeling around the infarcted area, whereas ISH of angiotensinogen displayed an overall low density in the myocardium with somewhat higher levels in the epicardium of sham and MI animals. Atrial natriuretic factor mRNA, a marker for cardiac hypertrophy, was approximately twofold higher in all compartments of the hearts after MI. The low amounts of renin and angiotensinogen mRNA in the noninfarcted hypertrophied myocardium indicate that the intracardiac synthesis of these components does not play a dominant role in the development of cardiac hypertrophy in the rat heart after MI. In addition, the increased renin mRNA expression in the border zone of the infarcted LV suggests a role for intracardiac angiotensin II in infarct healin

Collagen remodeling after myocardial infarction in the rat heart.

In this study changes in the amount and distribution of types I and III collagen mRNA and protein were investigated in the rat heart after induction of a left ventricular myocardial infarction (MI). Sham operated rats served as controls. The animals were sacrificed at different time intervals after operation. Northern blotting of cardiac RNA and hybridization with cDNA probes for types I and III procollagen revealed a 5- to 15-fold increase in the infarcted left ventricle. Type III procollagen mRNA levels were already increased at day 2 after MI, whereas type I procollagen mRNA followed this response at day 4 after MI. This increase was sustained for at least 21 days in the infarcted left ventricle for type III procollagen mRNA, whereas type 1 procollagen mRNA levels were still elevated at 90 days after MI. In the noninfarcted right ventricle a 5- to 7-fold increase was observed for both type I and type III procollagen mRNA levels, but only at day 4 after MI. In the non-infarcted septum a transient increase was observed for type I procollagen mRNA from day 7-21 (4- to 5-fold increase) and a decline to sham levels thereafter. In the septum type III procollagen mRNA levels were only elevated at 7 days after MI (4- to 5-fold increase) compared with sham operated controls. In situ hybridization with the same types I and III procollagen probes showed procollagen mRNA-producing cells in the infarcted area around necrotic cardiomyocytes, and in the interstitial cells in the non-infarcted part of the myocardium. No labeling was detected above cardiomyocytes. Combined in situ hybridization and immunohistochemistry showed that the collagen mRNA producing cells have a myofibroblast-like phenotype in the infarcted myocardium and are fibroblasts in the noninfarcted septum and right ventricle. The increase in types I and III procollagen mRNA in both infarcted and non-infarcted myocardium was followed by an increased collagen deposition, measured by computerized morphometry on sirius red-stained tissue sections as well as by the hydroxyproline assay. In the non-infarcted septum and right ventricle the collagen-positive area was maximal at day 14 (3- to 5-fold increase compared with sham operated controls) and slightly declined at day 21. In the infarcted myocardium the collagen-positive area was 57 +/- 10% at day 14 after MI. Hydroxyproline contents were significantly increased in the noninfarcted septum.(ABSTRACT TRUNCATED AT 400 WORDS

Activation of angiotensin-converting enzyme expression in infarct zone following myocardial infarction

In the present study we quantified angiotensin-converting enzyme (ACE) mRNA and localized ACE mRNA and protein in the infarcted rat heart. Wistar rats underwent ligation of the left descending coronary artery, resulting in myocardial infarction (MI) or a sham operation. At different times (1-90 days) after surgery (n = 3 each), the heart was removed and divided into the right ventricle (RV), septum (Se) and left ventricle (LV). ACE mRNA was quantified by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). At 4 and 7 days after MI, we found a 2.8-fold increase of ACE mRNA (n = 3; P <or = 0.05) in the infarcted LV compared with the LV of the sham group. No increases of ACE mRNA were found in the noninfarcted hypertrophied compartments. ACE activity increased 2.6- and 3.6-fold in the infarcted LV at 7 and 90 days after MI, respectively. In situ hybridization and immunohistochemistry showed increased ACE mRNA and protein density in the border zone of the infarcted area, predominantly in the endothelial cells lining capillaries. In the noninfarcted myocardium ACE mRNA and protein were confined to endothelial cells of the larger vessels. From these data we conclude that the intracardiac RAS is involved in the healing of the scar after MI in the rat, possibly giving rise to neovascularization. Furthermore, the data suggest that the intracardiac ACE is not necessarily associated with hypertrophy in the rat heart after M

A homologue of Drosophila tissue polarity gene frizzled is expressed in migrating myofibroblasts in the infarcted rat heart

Myocardial infarction results in the formation of granulation tissue in the injured ventricular wall. This tissue contains myofibroblasts in highly organized arrays; their contractile properties may help to prevent the infarct area from dilatation. The mechanisms that control myofibroblast alignment are unknown. We found that myofibroblasts express a homologue of Drosophila tissue polarity gene frizzled (fz2) when migrating into the granulation tissue. The expression is decreased after the cells have aligned. This suggests that fz2 is involved in the spatial control of cardiac wound repair after infarction, possibly through intra- and intercellular transmission of polarity signals as in developing Drosophila. Mutations in the fz2 gene may impair myofibroblast alignment in the infarct area, thereby resulting in ventricular dilatation and aneurism following infarctio

Morphological changes of the venous system in uremic patients. A histopathologic study

Because of the decreased venous compliance in hypertensive dialysis patients, it was investigated whether their venous system exhibited structural abnormalities. Venous samples were taken during transplantation from the common and external iliac vein in 12 hypertensive and 6 normotensive uremic patients and from the distal inferior caval vein and the common iliac vein in 7 kidney donors and 5 autopsy patients without history of cardiovascular disease. The thickness of the venous media was significantly increased in hypertensive uremic patients as compared to controls, but did not differ between normotensive patients and controls. The quantity of medial collagen did not differ among the various groups. The smooth muscle content of the media was increased in 5 uremic patients (2 normotensive and 3 hypertensive patients), whereas almost no smooth muscle was observed in the media of controls. Intimal thickening was observed neither in uremic patients nor in controls. In conclusion: increased medial thickness in hypertensive dialysis patients could be an explanation for the decreased venous compliance previously found in these patient

Lessons learned from a textbook outbreak: EHEC-O157:H7 infections associated with the consumption of raw meat products, June 2012, Limburg, Belgium.

&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;On 5 June 2012 several enterohemorrhagic Escherichia coli, EHEC, O157:H7 infections were reported to the public health authorities of Limburg.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;We performed a case-control study, a trace back/forward investigation and compared strains isolated from human cases and food samples. A case was defined as anyone with a laboratory-confirmed E. coli O157:H7-infection in North-East Limburg from May 30 2012 till July 15 2012. Family members with bloody diarrhea were also included as cases. E. coli O157 was isolated by culture and the presence of the virulence genes was verified using (q)PCR. Isolates were genotyped and compared by Pulsed Field Gel Electrophoresis (PFGE) and insertion sequence 629-printing (IS629-printing).&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;The outbreak involved 24 cases, of which 17 were laboratory-confirmed. Five cases developed Hemolytic Uremic Syndrome (HUS) and fifteen were hospitalized. Cases reported a significantly higher consumption of &quot;steak tartare&quot;, a raw meat product (OR 48.12; 95% CI; 5.62- 416.01). Cases were also more likely to buy meat-products at certain butcheries (OR 11.67; 95% CI; 1.41 - 96.49). PFGE and IS629-printing demonstrated that the vtx1a vtx2a eae ehxA positive EHEC O157:H7 strains isolated from three meat products and all seventeen human stool samples were identical. In a slaughterhouse, identified by the trace-back investigation, a carcass infected with a different EHEC strain was found and confiscated.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSION: &lt;/b&gt;We present a well described and effectively investigated foodborne outbreak associated with meat products. Our main recommendations are the facilitation and acceleration of the outbreak detection and the development of a communication plan to reaches all persons at risk.&lt;/p&gt;&lt;p&gt;&lt;b&gt;MESH: &lt;/b&gt;Foodborne diseases, Shiga-toxigenic Escherichia coli, Enterohemorrhagic Escherichia coli, Meat products, Case control studies, Electrophoresis, Gel, Pulsed-Field.&lt;/p&gt;</p