assessment-cardiac-function-myocardial-morphology-using-small-animal

Assessment of Cardiac Function and Myocardial Morphology Using Small Animal Look-locker Inversion Recovery (SALLI) MRI in Rats

Small animal magnetic resonance  imaging is an important tool to study cardiac function and changes in myocardial  tissue. The high heart rates of small ...

German Heart Institute Berlin

We investigated the effects of treatment with the angiotensin II type 1 receptor antagonist, telmisartan, on abdominal aortic aneurysm formation in normotensive rats.

Telmisartan prevents aneurysm progression in the rat by inhibiting proteolysis, apoptosis and inflammation.

Nous avons &eacute;tudi&eacute; les effets du traitement par l&#39;antagoniste du r&eacute;cepteur 1 de l&#39;angiotensine II type, telmisartan, sur la formation de l&#39;an&eacute;vrisme de l&#39;aorte abdominale chez les rats normotendus.

Telmisartan emp&ecirc;che la progression d&#39;an&eacute;vrisme chez le rat en inhibant la prot&eacute;olyse, l&#39;apoptose et l&#39;inflammation.

Abbiamo studiato gli effetti del trattamento con angiotensina II tipo 1 recettore antagonista, telmisartan, sulla formazione di aneurisma dell&#39;aorta addominale nei ratti normotesi.

Telmisartan impedisce la progressione di aneurisma nel ratto inibendo la proteolisi, l&#39;apoptosi e l&#39;infiammazione.

While the renin-angiotensin system (RAS) is widely recognized to be involved in atherosclerosis, its potential role in the progression from atherosclerotic lesions to abdominal aortic aneurysm (AAA) is poorly understood. The present study aimed to investigate which components of the RAS may render the atherosclerotic aorta aneurysmatic. The expression of renin, prorenin/renin receptor, angiotensinogen, AT1- and AT2 receptors, cathepsin D, cathepsin G and chymase was examined by immunoblotting and immunohistochemistry in human atherosclerotic, aneurysmatic and healthy aortic tissues obtained from patients undergoing elective repair or at autopsy. AT1- and AT2 receptor mRNA expression was determined using quantitative real-time RT-PCR. All investigated local RAS components were up-regulated in atherosclerotic as compared to healthy tissues. AAA compared to atherosclerosis was characterized by a further increase in the expression of all RAS components except for the AT2 receptor. Cathepsin D was exclusively up-regulated in AAA. Most RAS components co-localized with infiltrating leukocytes or mast cells pointing to their contribution to inflammatory processes. Due to their proteolytic features, some RAS components (cathepsin D and cathepsin G and chymase) may contribute to AAA formation by accessory mechanisms. Taken together, our data suggest that in humans, RAS activation is not just a key-player in the pathogenesis of atherosclerosis, but that a further increasing activation may be involved in the transition from atherosclerosis to AAA.

Transition from atherosclerosis to aortic aneurysm in humans coincides with an increased expression of RAS components.

Alors que le syst&egrave;me r&eacute;nine-angiotensine (RAS) est largement reconnu pour &ecirc;tre impliqu&eacute;s dans l&#39;ath&eacute;roscl&eacute;rose, son r&ocirc;le potentiel dans la progression de l&eacute;sions ath&eacute;roscl&eacute;reuses vers l&#39;aorte abdominale (AAA) est mal comprise. La pr&eacute;sente &eacute;tude visait &agrave; examiner quels composants du RAS peuvent invalider l&#39;aorte ath&eacute;romateuse an&eacute;vrismale. L&#39;expression de la r&eacute;nine, r&eacute;cepteurs pror&eacute;nine/r&eacute;nine, l&#39;angiotensinog&egrave;ne, r&eacute;cepteurs AT1 et AT2, cathepsine D, cathepsine G et chymase fut examin&eacute;e par immunotransfert et immunohistochimie in human tissues ath&eacute;roscl&eacute;reuses, sains et an&eacute;vrismale aortiques obtenus de patients subissant une r&eacute;paration &eacute;lective ou lors de l&#39;autopsie. Expression des ARNm de r&eacute;cepteurs AT1 et AT2 a &eacute;t&eacute; d&eacute;termin&eacute;e &agrave; l&#39;aide de RT-PCR quantitative en temps r&eacute;el. Tous les composants &eacute;tudi&eacute;s des RAS les ont &eacute;t&eacute; r&eacute;gul&eacute;e en ath&eacute;roscl&eacute;rose par rapport aux tissus sains. AAA par rapport &agrave; l&#39;ath&eacute;roscl&eacute;rose se caract&eacute;rise par une nouvelle augmentation de l&#39;expression de tous les composants RAS sauf pour le r&eacute;cepteur AT2. Cathepsine D &eacute;tait exclusivement r&eacute;gul&eacute;e en AAA. La plupart des composants RAS co-localisaient avec infiltration de leucocytes ou mastocytes pointant sur leur contribution au processus inflammatoires. En raison de leurs caract&eacute;ristiques prot&eacute;olytiques, certains composants RAS (cathepsine D et cathepsine G et chymase) peuvent contribuer &agrave; formation AAA par les m&eacute;canismes de l&#39;accessoires. Ensemble, nos r&eacute;sultats sugg&egrave;rent que chez les humains, activation de RAS n&#39;est pas juste un joueur cl&eacute; dans la pathogen&egrave;se de l&#39;ath&eacute;roscl&eacute;rose, mais qu&#39;une activation plus croissante pourrait &ecirc;tre impliqu&eacute;e dans la transition entre l&#39;ath&eacute;roscl&eacute;rose et AAA.

Transition entre l&#39;ath&eacute;roscl&eacute;rose et an&eacute;vrisme aortique chez l&#39;homme co&iuml;ncide avec une augmentation de l&#39;expression des composantes de la RAS.

Mentre il sistema renina-angiotensina (RAS) &egrave; ampiamente riconosciuto per essere coinvolti nella aterosclerosi, suo ruolo potenziale nella progressione da lesioni aterosclerotiche per aneurisma dell&#39;aorta addominale (AAA) &egrave; poco conosciuta. Il presente studio mira a indagare quali componenti della RAS possono rendere l&#39;aorta aterosclerotica aneurysmatic. L&#39;espressione della renina, recettore Aer/renina, angiotensinogen, i recettori AT1 e AT2, catepsina D, catepsina G e chymase &egrave; stato esaminato da immunoblotting e immunoistochimica in aterosclerotici, aneurysmatic e sani aortico tessuti umani ottenuti da pazienti sottoposti a riparazione elettiva o all&#39;autopsia. Espressione del mRNA del recettore AT1 e AT2 &egrave; stata determinata mediante RT-PCR quantitativa in tempo reale. Componenti RAS studiati tutti i locali sono up-regolate in aterosclerotica rispetto ai tessuti sani. AAA rispetto all&#39;aterosclerosi &egrave; stata caratterizzata da un ulteriore aumento di espressione di tutti i componenti RAS, fatta eccezione per il recettore AT2. Catepsina D era esclusivamente regolato in AAA. La maggior parte dei componenti RAS co-ha localizzati con infiltrazione dei leucociti o mastociti che punta al loro contributo ai processi infiammatori. A causa della loro funzionalit&agrave; proteolitici, alcuni componenti RAS (catepsina D e catepsina G e chymase) possono contribuiscono alla formazione di AAA da meccanismi accessori. Presi insieme, i nostri dati suggeriscono che negli esseri umani, attivazione di RAS non &egrave; solo un giocatore chiave nella patogenesi dell&#39;aterosclerosi, ma che un ulteriore aumento di attivazione pu&ograve; essere coinvolto nella transizione da aterosclerosi a AAA.

Transizione da aterosclerosi per aneurisma aortico in esseri umani coincide con un&#39;aumentata espressione di componenti RAS.

The cannabinoid receptors, CB1 and CB2, are expressed in the heart, but their role under pathological conditions remains controversial. This study examined the effect of CB1 receptor blockade on cardiovascular functions after experimental MI and in experimental metabolic syndrome. MI was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with the CB1 receptor antagonist rimonabant (10Â mg/kg i.p. daily) started 7Â days before or 6Â h after MI and continued for 6Â weeks. Haemodynamic parameters were measured via echocardiography and intracardiac Samba catheter. CB1 blockade improved systolic and diastolic heart function, decreased cardiac collagen and hydroxyproline content and down-regulated TGF-Î²1. Additionally, rimonabant decreased arterial stiffness, normalised QRS complex duration and reduced brain natriuretic peptide levels in serum. In primary cardiac fibroblasts, rimonabant decreased MMP-9 activity and TGF-Î²1 expression. Furthermore, rimonabant improved depressed systolic function of spontaneously hypertensive obese rats and reduced weight gain. Blocking of CB1 receptor with rimonabant improves cardiac functions in the early and late stages after MI, decreases arterial stiffness and reduces cardiac remodelling. Rimonabant also has cardioprotective actions in rats characterised by the metabolic syndrome. Inhibition of proteolysis and TGF-Î²1 expression and reduced collagen content by rimonabant may attenuate destruction of the extracellular matrix and decrease fibrosis after MI.

Cannabinoid receptor 1 inhibition improves cardiac function and remodelling after myocardial infarction and in experimental metabolic syndrome.

Les r&eacute;cepteurs cannabino&iuml;des CB1 et CB2, sont exprim&eacute;es dans le coeur, mais leur r&ocirc;le dans des conditions pathologiques demeure controvers&eacute;. Cette &eacute;tude a examin&eacute; l&#39;effet du blocage des r&eacute;cepteurs CB1 sur les fonctions cardiovasculaires apr&egrave;s MI exp&eacute;rimental et au syndrome m&eacute;tabolique exp&eacute;rimental. MI a &eacute;t&eacute; induite chez des rats Wistar par permanente ligature de l&#39;art&egrave;re coronaire gauche. Traitement avec le CB1 r&eacute;cepteur antagoniste rimonabant (i.p. 10 mg/kg par jour) a commenc&eacute; &agrave; 7 jours avant ou 6 h apr&egrave;s MI et a continu&eacute; pendant 6 semaines. Param&egrave;tres h&eacute;modynamiques ont &eacute;t&eacute; mesur&eacute;s par &eacute;chocardiographie et cath&eacute;ter intracardiaque de Samba. CB1 blocus am&eacute;lior&eacute; systolique et de la fonction cardiaque diastolique, a diminu&eacute; de collag&egrave;ne cardiaque et l&#39;hydroxyproline contenu et TGF-&beta;1 diminu&eacute;es. En outre, le rimonabant a diminu&eacute; la rigidit&eacute; art&eacute;rielle, normalis&eacute;e dur&eacute;e complexe QRS et taux de peptide natriur&eacute;tique c&eacute;r&eacute;brale r&eacute;duite dans le s&eacute;rum. Dans les fibroblastes cardiaques primaires, rimonabant diminue l&#39;activit&eacute; MMP-9 et l&#39;expression de TGF-&beta;1. En outre, rimonabant am&eacute;lior&eacute; d&eacute;prim&eacute; fonction systolique des rats ob&egrave;ses spontan&eacute;ment hypertensifs et r&eacute;duction du gain de poids. Blocage des r&eacute;cepteurs CB1 avec rimonabant am&eacute;liore les fonctions cardiaques dans les stades pr&eacute;coces et tardifs apr&egrave;s MI, diminue la rigidit&eacute; art&eacute;rielle et r&eacute;duit le remodelage cardiaque. Rimonabant a &eacute;galement un effet cardioprotecteur des actions chez les rats caract&eacute;ris&eacute;es par le syndrome m&eacute;tabolique. L&#39;inhibition de la prot&eacute;olyse et expression de TGF-&beta;1 et contenu par rimonabant r&eacute;duit collag&egrave;ne peut att&eacute;nuer la destruction de la matrice extracellulaire et diminuer la fibrose apr&egrave;s MI.

Inhibition des r&eacute;cepteurs 1 cannabino&iuml;de am&eacute;liore la fonction cardiaque et remodelage apr&egrave;s infarctus du myocarde et dans le syndrome m&eacute;tabolique exp&eacute;rimental.

Article	Year
Telmisartan prevents aneurysm progression in the rat by inhibiting proteolysis, apoptosis and inflammation. Journal of hypertension\| PubMed ID: 19008714	2008
Transition from atherosclerosis to aortic aneurysm in humans coincides with an increased expression of RAS components. Atherosclerosis\| PubMed ID: 19193379	2009
Cannabinoid receptor 1 inhibition improves cardiac function and remodelling after myocardial infarction and in experimental metabolic syndrome. Journal of molecular medicine (Berlin, Germany)\| PubMed ID: 23636507	2013

Ulrich Kemnitz

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