Inflammation and ECM (extracellular matrix) remodelling play important roles in LV (left ventricular) remodelling following acute MI (myocardial infarction). Previous studies show elevated plasma MMP (matrix metalloproteinase) levels in patients with acute MI, but their sources are not clear. The recruitment of mononuclear cells into the infarcted myocardium is critical for inflammatory responses, but their exact roles in LV remodelling have not been fully investigated, as it is difficult to isolate and study the function of regional inflammatory cells. To address these questions, we isolated PBMCs (peripheral blood mononuclear cells) from blood samples of patients with acute MI or stable angina, or healthy controls ( n =14, 8 and 12 respectively). PBMCs were cultured for 24 h and the MMP9 level in the culture medium was measured by gelatin zymography, and MMP9 gene expression was measured by real-time PCR. Two superarrays (ECM and adhesion molecules, and common cytokines; 84 genes included in each array) were employed to screen gene expression profiles by PBMCs in five patients with acute MI and five controls. We found that MMP9 expression by PBMCs at both the mRNA and protein levels was increased 2-fold (both P <0.05) in patients with acute MI compared with the two control groups. Notably, MMP2 was not expressed by PBMCs. Superarray screening revealed that PBMCs not only expressed MMPs, TIMPs (tissue inhibitors of metalloproteinases) and matrix proteins, but also served as an important source of cell adhesion molecules, inflammatory cytokines and growth factors. A total of 42 genes were differentially expressed in patients with acute MI compared with controls. Expression of selected genes was confirmed by real-time PCR. In conclusion, PBMCs constitute a key cellular source for elevated plasma MMP9, but not for MMP2. PBMCs also contribute to systemic and regional inflammation and matrix remodelling in acute MI.

The mechanism of cardiac rupture after MI (myocardial infarction) is not fully understood. Rupture has not been reported in most laboratory species, including the rat, but does occur in mice. We have reported previously that β 2 -TG mice (transgenic mice with cardiac-restricted overexpression of β 2 -adrenergic receptors) had a lower incidence of rupture compared with NTG (non-transgenic) littermates. We hypothesized that the difference in the incidence of rupture between rodents and specific mouse strains is due to the difference in collagen content following MI. In the present study, we compared the difference in matrix remodelling post-MI between β 2 -TG and NTG mice and between mice and rats. MI was induced by ligation of the left main coronary artery. Following MI, tensile strength, insoluble and soluble collagen content and gelatinase expression were determined in the infarcted and non-infarcted myocardium. Better preserved tensile strength measured as TTR [tension-to-rupture; 88±14 and 58±3% of the respective sham group values for β 2 -TG compared with NTG mice ( P <0.05); 108±7 and 32±4% of the respective sham group values for rats compared with 129sv mice ( P <0.01)] and less severe acute infarct expansion after MI were found in rats compared with mice or in β 2 -TG compared with NTG mice. These differences were associated with a higher content of pre-existing fibril collagen in the normal myocardium of β 2 -TG compared with NTG mice (1.6-fold) or rats compared with 129sv mice (2-fold) and an accelerated fibrotic healing in the infarcted myocardium. Additionally, a less pronounced increase in MMP-9 (matrix metalloproteinase-9) activity was observed in the infarcted myocardium of rats compared with 129sv mice. We conclude that a higher collagen level is associated with facilitated fibrotic healing of an infarct and preserves the tensile strength of infarcted myocardium, thereby preventing cardiac rupture and acute ventricular remodelling.

Contrast media can induce both a decrease in renal blood flow and a reduction in glomerular filtration rate (GFR) when administered to both experimental animals and humans. In the present study we have examined the role of adenosine in mediating these effects using the isolated perfused rat kidney. Kidneys were perfused with a 6.7%-(w/v)-albumin-based perfusate supplemented with glucose and amino acids ( n = 6 per group). They were exposed to diatrizoate [20 mg of iodine (mgI)/ml; osmolality 1650 mOsm/kg of water] or iotrolan (20 mgI/ml; osmolality 320 mOsm/kg of water) in the presence or absence of theophylline (10.8 µ g/ml), or to diatrizoate in the presence or absence of a specific adenosine A 1 receptor antagonist (KW-3902; 2 µ g/ml) or a specific A 2 receptor antagonist (KF17837; 6 µ g/ml). Diatrizoate ( n = 6) produced a fall in GFR from 0.65±0.04 to 0.42±0.03 ml·min -1 ·g -1 ( P < 0.05); renal perfusate flow (RPF) also declined, from 36.5±3.8 to 22.0±3.2 ml·min -1 ·g -1 ( P < 0.05). Iotrolan ( n = 6) produced a fall in GFR from 0.64±0.02 to 0.48±0.04 ml·min -1 ·g -1 ( P < 0.05) and in RPF from 33.3±3.8 to 24.0±3.0 ml·min -1 ·g -1 ( P < 0.05). Theophylline (10.8 µ g/ml) prevented the fall in GFR caused by either diatrizoate (baseline, 0.63±0.05 ml·min -1 ·g -1 ; diatrizoate+theophylline, 0.60±0.04 ml·min -1 ·g -1 ) or iotrolan (basline, 0.64±0.04 ml·min -1 ·g -1 ; iotrolan+theophylline, 0.67±0.05 ml·min -1 ·g -1 ), but did not affect the decreases in RPF caused by either agent. KW-3902 (2 µ g/ml) also prevented the fall in GFR produced by diatrizoate (baseline, 0.66±0.05 ml·min -1 ·g -1 ; diatrizoate+KW-3902, 0.61±0.05 ml·min -1 ·g -1 ), while the fall in RPF remained unaffected. KF17837 (6 µ g/ml) had no effect on the decreases in either GFR or RPF induced by diatrizoate ( n = 6 per group). The results suggest a role for adenosine acting at the A 1 receptor in mediating the decrease in GFR induced by contrast media. This effect is independent of a change in renal vascular resistance, and possibly secondary to mesangial cell contraction causing a decrease in the ultrafiltration coefficient.