Following a severe ischemic injury or
myocardial infarction, the extracellular matrix (ECM) of the heart is involved in pathophysiological conditions such as dilatation and cardiac dysfunction.
Osteopontin (OPN) has been shown to interact with
fibronectin suggesting its possible role in matrix organization, stability and wound healing. There is increased expression of OPN in several tissues in response to injury. Therefore, we tested the hypothesis that acute
ischemia (2 h), followed by reperfusion (4 h) may induce early OPN and
fibronectin in an isolated hemoperfused working porcine heart model. Twenty hearts were prepared and connected to a perfusion system. After 1 h of perfusion, these hearts were randomized to two groups: ten infarcted (MI, ramus circumflexus) and ten non-infarcted hearts (C). In addition, cardiac fibroblasts derived from infarcted, remote and control myocardium were investigated. In both groups, the heart rate,
electrolytes, pH, blood
gases, and
lactate remained similar. The LVEDP and perfusion pressure of MI hearts increased significantly (P<0.05). The total
fibronectin and OPN volume contents were clearly elevated in the
infarct area. The
matrix metalloproteinases (MMP-1 and MMP-8),
fibronectin, OPN,
TGF-beta1 proteins and the mRNAs for
fibronectin,
TGF-beta1, and OPN were significantly elevated in the
infarct area as compared to the remote area and the non-infarcted hearts. Simultaneously, circulating carboxyterminal propeptide of
type I procollagen (
PICP) was released in the perfusion medium (threefold versus C). Fibroblast-like cells originating from the
infarct area exhibited an enhanced OPN and
fibronectin gene and
protein expression compared to fibroblasts derived from control myocardium. Our data demonstrate the early appearance of the
MMPs (increased
collagen degrading
enzymes) and
PICP (a
collagen synthesis marker) following
ischemia and reperfusion. Moreover, OPN,
fibronectin and
TGF-beta1 protein and gene expression are elevated after
ischemia and reperfusion in the ex vivo working hemoperfused porcine heart model.