Cellular and molecular mechanisms?

Præsentationer af emnet: "Cellular and molecular mechanisms?"— Præsentationens transcript:

1 Cellular and molecular mechanisms?
Henning Bundgaard The Heart Center Rigshospitalet

2 The inherited cardiac diseases
Cardiomyopathies: Hypertrophic, dilated, idiopathic restrictive and arrhythmogenic right ventricle cardiomyopathy, non-compaction, muscular dystrophies Channelopathies: Long QT syndrome, Brugada syndrome, Catecholaminergic polymorf VT Ischaemic heart disease: Premature IHD, familial hypercholesterolemia Storage diseases: Hereditary hemochromatosis, familial amyloidosis, Fabry disease Others: Pulmonary arterial hypertension, Marfan syndrome Sudden cardiac death: +…+…+…

3                                                                             <> McKenna W.

4 ARVC – fat in RV

5 Dilated cardiomyopathy

6 Restrictive cardiomyopathy

7                                                                             <> McKenna W.

8 Intercalated discs in normal heart
Athlete’s heart HCM LV wall thickness + Unusual LVH patterns - + LV d cavity < 45 mm - - LV d cavity > 55 mm + + Marked LA enlargement - + Bizarre ECG patterns - + Abnormal LV filling - + Female sex - -  Wall after deconditioning + + Family history of HCM - - Max VO2 > 45 ml/kg/min + HCM Grey zone; 13-15 mm Athlete’s heart Maron BJ, Heart, 2005

9                                                                             <> McKenna W.

10 Arrhythmogenic right ventricular cardiomyopathy

11 Dilated cardiomyopathy

12                                                                             <> Spirito et al.

13 Desmosomal diseases - ARVC

14 Desmosomal diseases - ARVC

15 Desmosomal diseases

16 Desmosomal diseases - ARVC
Mutations in genes that can cause DCM EHJ, Osterziel, 2005

17 Cell communications

18 Ion-channel diseases

19 Ion-channel diseases

20 Ionic Hypothesis

21 [Ca2+]  [Na+]  Ionic Hypothesis [Ca2+]  [Ca2+] Time Normal
Heart Failure [Ca2+] Time Normal

22 +

23

24 Noradrenaline

25 DM Bers. Cardiac E-C Coupling. 2001
60 70 80 90 100 110 120 130 140 150 160 5 7 9 11 13 15 17 19 [Na]i Contractility (% control)

26                                                                             <> McKenna W.

27                                                                             <>

28 Sammenfatning Med genetikken – og dermed molekylærbiologien - tager vi et dybt spadestik ned i de normale og de patologiske mekanismer i cellen – vidtgående ukendt land Vi kan se frem til nye ”tailored” og revolutionerende behandlingsmuligheder baseret på molekylærbiologien Vi har umådeligt meget at lære endnu

29 Take home message 1 = 4 (1 proband + 3 relatives)