["Why is it always the heart which suffers from myocardial infarction?" The "Marburg hypothesis" of the pathogenesis of atherosclerosis].
There is no question that cholesterol, especially low-density lipoprotein (LDL) cholesterol, represent a major cardiovascular risk factor. The so-called lipid hypothesis has been proven by almost all epidemiologic studies, animal studies and, most importantly, by interventional studies with lipid-lowering drugs, especially statins. However, despite our better understanding of atherogenesis we cannot explain why atherosclerosis occurs most frequently and severely on coronary arteries rather than on other arteries such as those of the hands or feet. In addition, the "lipid hypothesis" is unable to explain the dramatic change in severity of a far more generalized atherosclerosis in patients suffering from diabetes mellitus.Recently, we studied the effects of fatty acids on endothelial integrity and found a dramatic increase in apoptosis under fatty acid exposition. Since it is well known that the heart depends highly on fatty acid delivery to cover its energy demand, we hypothesize that the heart becomes the victim of its energy demand. With the so-called Marburg hypothesis of atherogenesis we can explain the fact why especially the arteries of the heart show early atherosclerotic lesions, but also the fact why patients with diabetes develop more generalized atherosclerosis. Finding mechanisms to reduce the presence of fatty acids within the arterial wall might prevent plaque destabilization and could be a potential target in our fight against atherosclerosis.
Memoriam Klumpp
In Frau Susanne
IF
Zentrum Innere Medizin-Kardiologie, Universitätsklinikum Giessen-Marburg, Philipps-Universität Marburg, Marburg, Germany. Juergen.schaefer@staff.uni-marburg.de
Schaefer
Jürgen R
JR
Hufnagel
Birgit
B
Maisch
Bernhard
B
Krieglstein
Josef
J
D050197:Atherosclerosis / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
D005227:Fatty Acids
J Intern Med. 2009 Jun;265(6):689-97
19226374
Lancet. 2005 Nov 26;366(9500):1849-61
16310551
Eur Heart J. 2010 Jan;31(1):92-9
19797259
Fundam Clin Pharmacol. 2010 Aug;24(4):469-76
20030737
Atherosclerosis. 2005 Jun;180(2):245-54
15910849
Nature. 2000 Sep 14;407(6801):233-41
11001066
Nature. 2002 Dec 19-26;420(6917):868-74
12490960
J Clin Endocrinol Metab. 2006 Jul;91(7):2542-7
16595593
Eur J Clin Invest. 2007 Oct;37(10):774-82
17888088
Nat Rev Drug Discov. 2002 Feb;1(2):122-30
12120093
Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):1904-9
15319266
Atherosclerosis. 2005 Jun;180(2):417-8
15910870
J Lipid Res. 1994 Jul;35(7):1152-60
7525821
Neurochem Int. 2003 Jun;42(7):555-60
12590938
FEBS Lett. 1998 Oct 23;437(3):229-32
9824296
J Clin Invest. 1992 Feb;89(2):373-80
1737833
Nat Med. 2002 Nov;8(11):1249-56
12411952