Short-term myocardial ischemia induces cardiac modified  C-reactive protein expression and proinflammatory gene  (cyclo-oxygenase-2, monocyte chemoattractant protein-1, and  tissue factor) upregulation in peripheral blood mononuclear  cells.
BACKGROUND
Prompt coronary thrombus resolution, reducing time of ischemia, improves cardiac recovery. The factors triggered by ischemia that contribute to the clinical outcome are not fully known. We hypothesize that unabated inflammation due to cardiac ischemia may be a contributing factor.


OBJECTIVE
As a proof-of-concept, we evaluated the effect of short-term myocardial ischemia on the local and systemic inflammatory response.


METHODS
Pigs underwent either 90-min mid-left anterior descending (LAD) coronary artery balloon occlusion (infarct size 25% +/- 1% left ventricle; 29% heart function deterioration) or a sham-operation procedure. Peri-infarcted and non-ischemic cardiac tissue was obtained for histopathologic, molecular and immunohistochemical analysis of inflammatory markers [interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), modified C-reactive protein (mCRP), and human alveolar macrophage-56 (HAM-56)]. Blood (femoral vein) was withdrawn prior to myocardial infarction (MI) induction (t = 0) and at 30 and 90 min to evaluate: (i) systemic cytokine levels (IL-6, TNF-alpha, CRP); (ii) proinflammatory gene and protein expression in peripheral blood mononuclear cells (PBMCs) of tissue factor (TF), cyclo-oxygenase-2 (Cox-2), monocyte chemoattractant protein-1 (MCP-1), and CRP; and (iii) platelet activation (assessed by perfusion studies and RhoA activation).


RESULTS
Short-term ischemia triggered cardiac IL-6 and TNF-alpha expression, recruitment of inflammatory cells, and mCRP expression in infiltrated macrophages (P < 0.05 vs. t = 0 and sham). PBMC mRNA and protein expression of MCP-1, Cox-2 and TF was significantly increased by ischemia, whereas no differences were detected in CRP. Ischemia increased cardiac troponin-I, IL-6 and TNF-alpha systemic levels, and was associated with higher platelet deposition and RhoA activation (P < 0.001 vs. t = 0 and sham).


CONCLUSIONS
Short-term myocardial ischemia, even without atherosclerosis, induces an inflammatory phenotype by inducing local recruitment of macrophages and systemic activation of mononuclear cells, and renders platelets more susceptible to activation.
Vilahur
G
G
Cardiovascular Research Centre, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Hernández-Vera
R
R
Molins
B
B
Casaní
L
L
Duran
X
X
Padró
T
T
Badimon
L
L
D000818:Animals; D015415:Biomarkers; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines; D007107:Immune System / Q000166:cytology; D007155:Immunologic Factors / Q000235:genetics* / Q000378:metabolism; D007249:Inflammation; D017202:Myocardial Ischemia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015539:Platelet Activation; D013552:Swine; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
D015415:Biomarkers; D018932:Chemokine CCL2; D016207:Cytokines; D007155:Immunologic Factors; D002097:C-Reactive Protein; D013925:Thromboplastin; D051546:Cyclooxygenase 2