Tissue inhibitor of matrix metalloproteinase-1 in norepinephrine-induced remodeling of the mouse heart.
BACKGROUND
Matrix metalloproteinases (MMPs) play an important role in myocardial remodeling. Their activity is regulated by the tissue inhibitors of metalloproteinases (TIMPs). The present study analyzed the contribution of changes in functional and molecular parameters to early cardiac remodeling in mice hearts. The role that TIMPs might play in this process was specially acknowledged.


METHODS
The remodeling was induced by norepinephrine (NE) given sc in balb/c mice. Varying concentrations, time and the addition of a neutralizing TIMP-1 antibody were evaluated.


RESULTS
High dose NE led to insufficiency of the left ventricle (LV) as evidenced by reduced NE-induced elevation of LV systolic pressure, contractility and relaxation. Further, signs of lung congestion were seen. NE induced a concentration-dependent increase of LV weight/body weight (LVW/BW) ratio and elevated mRNA expression of atrial natriuretic peptide (ANP). This was accompanied by induction of collagen type I and III, as well as TIMP-1 expression.


CONCLUSIONS
The NE-induced increase of TIMP-1 expression may induce the elevation of the antihypertrophic cardiac factor ANP since NE-induced increase of ANP expression was abolished by neutralizing TIMP-1 antibody. Thus, TIMP-1 may mediate ANP-induced attenuation of NE-induced hypertrophy in the mouse heart.
Meier
Henning
H
Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany.
Bullinger
Jorg
J
Deten
Alexander
A
Marx
Grit
G
Rabald
Steffen
S
Zimmer
Heinz-Gerd
HG
Briest
Wilfried
W
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009638:Norepinephrine / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000187:drug effects*
D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D009638:Norepinephrine