Regarding the concept of MMP-9s being responsible for most myelin damage, I must confess that I have never really given all the TIMPs-1 a clean bill of health.
They are suppose to insure that the MMP-9s only eat the BAD STUFF.(dead/damaged/dying things)
What if they are at fault and are directing the MMP-9s to the Myelin for LUNCH?????
Traitors for sure - but is there reasonable evidence to even suspect them???
I can imagine that transplanting some "Right-thinking/Right-Acting" TIMP-1 producing genes that generate TIMP-1s which are proven MYELIN PROTECTORS would also be a good idea.
(I reserve the rights of Intellectual Discovery despite this public posting here.)
1: Circulation. 2004 Sep 14;110(11 Suppl 1):II180-6.
Inhibition of matrix metalloproteinase activity by TIMP-1 gene transfer
effectively treats ischemic cardiomyopathy.
Jayasankar V, Woo YJ, Bish LT, Pirolli TJ, Berry MF, Burdick J, Bhalla RC,
Sharma RV, Gardner TJ, Sweeney HL.
Department of Surgery, University of Pennsylvania School of Medicine,
Philadelphia, Pa 19104-4283, USA
BACKGROUND: Enhanced activity of matrix metalloproteinases (MMPs) has been
associated with extracellular matrix degradation and ischemic heart failure in
animal models and human patients. This study evaluated the effects of MMP
inhibition by gene transfer of TIMP-1 in a rat model of ischemic cardiomyopathy.
METHODS AND RESULTS: Rats underwent ligation of the left anterior descending
coronary artery with direct intramyocardial injection of replication-deficient
adenovirus encoding TIMP-1 (n=8) or null virus as control vector (n=8), and
animals were analyzed after 6 weeks. Both systolic and diastolic cardiac
function was significantly preserved in the TIMP-1 group compared with control
animals (maximum left ventricular [LV] pressure: TIMP-1 70+/-10 versus control
56+/-12 mmHg, P<0.05; maximum dP/dt 2697+/-842 versus 1622+/-527 mmHg/sec,
P<0.01; minimum dP/dt -2900+/-917 versus -1195+/-593, P<0.001). Ventricular
geometry was significantly preserved in the TIMP-1 group (LV diameter 13.0+/-0.7
versus control 14.4+/-0.4 mm, P<0.001; border-zone wall thickness 1.59+/-0.11
versus control 1.28+/-0.19 mm, P<0.05), and this was associated with a reduction
in myocardial fibrosis (2.36+/-0.87 versus control 3.89+/-1.79 microg
hydroxyproline/mg tissue, P<0.05). MMP activity was reduced in the TIMP-1
animals (1.5+/-0.9 versus control 43.1+/-14.9 ng of MMP-1 activity, P<0.05).
CONCLUSIONS: TIMP-1 gene transfer inhibits MMP activity and preserves cardiac
function and geometry in ischemic cardiomyopathy. The reduction in myocardial
fibrosis may be primarily responsible for the improved diastolic function in
TIMP-1 overexpression is a promising therapeutic target for
PMID: 15364860 [PubMed - indexed for MEDLINE]