Key result
Norepinephrine-induced increase of ANP expression was abolished by a neutralizing TIMP-1 antibody, suggesting TIMP-1 mediates ANP-induced attenuation of hypertrophy in the mouse heart.
Why the study?
Does TIMP-1 mediate ANP expression in norepinephrine-induced cardiac remodeling in mice?
Does TIMP-1 mediate ANP expression in norepinephrine-induced cardiac remodeling in mice?
In a mouse model, TIMP-1 appears to mediate the elevation of the antihypertrophic factor ANP during norepinephrine-induced cardiac remodeling.
TIMP-1 may attenuate NE-induced hypertrophy via ANP in mice; leaves open its translational role in human remodeling.
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.
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Meier et al. (2007) studied Norepinephrine-induced cardiac remodeling. Norepinephrine and neutralizing TIMP-1 antibody was evaluated on Cardiac remodeling parameters including LV systolic pressure, contractility, relaxation, LVW/BW ratio, and ANP expression. Norepinephrine-induced increase of ANP expression was abolished by a neutralizing TIMP-1 antibody, suggesting TIMP-1 mediates ANP-induced attenuation of hypertrophy in the mouse heart.
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