Download Cellular and molecular mechanisms

Cellular and molecular
mechanisms?
Henning Bundgaard
The Heart Center
Rigshospitalet
The inherited cardiac diseases
1. Cardiomyopathies:
Hypertrophic, dilated, idiopathic restrictive and
arrhythmogenic right ventricle cardiomyopathy,
non-compaction, muscular dystrophies
2. Channelopathies:
Long QT syndrome, Brugada syndrome,
Catecholaminergic polymorf VT
3. Ischaemic heart disease:
Premature IHD, familial hypercholesterolemia
4. Storage diseases:
Hereditary hemochromatosis, familial amyloidosis,
Fabry disease
5. Others:
Pulmonary arterial hypertension, Marfan syndrome
6. Sudden cardiac death:
7. +…+…+…
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McKenna W.
ARVC – fat in RV
Dilated cardiomyopathy
Restrictive cardiomyopathy
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McKenna W.
Intercalated discs in normal heart
HCM
LV wall
thickness
HCM
Grey zone;
13-15 mm
Athlete’s
heart
Athlete’s
heart
+
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
+
Maron BJ, Heart, 2005
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McKenna W.
Arrhythmogenic right ventricular
cardiomyopathy
Dilated cardiomyopathy
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Spirito et al.
Desmosomal diseases - ARVC
Desmosomal diseases - ARVC
Desmosomal diseases
Desmosomal diseases - ARVC
Mutations in genes that can cause DCM.
EHJ, Osterziel, 2005
Cell communications
Ion-channel diseases
Ion-channel diseases
Ionic Hypothesis
Ionic Hypothesis
[Ca2+]] 
[Ca
[Na+] 
2+
Normal
Heart Failure
[Ca2+]
Time
+
Noradrenaline
DM Bers. Cardiac E-C Coupling. 2001
160
Contractility (% control)
150
140
130
120
110
100
90
80
70
60
5
7
9
11
13
[Na]i
15
17
19
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McKenna W.
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Sammenfatning
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
 Med
Take home message
1 = 4 (1 proband + 3 relatives)