Cardiac protection by pharmacological modulation of inflammation.
Inflammation is a reaction to primary injury of various kinds, such as infection and trauma, which has both beneficial and detrimental effects. Inflammation has been associated with major diseases of the heart and vessels. Research has focused not only on ischaemia but also on post-ischaemic reperfusion, which is known to activate and amplify the inflammatory response. Although reperfusion should always be attempted in the clinical environment, it has been shown experimentally that it can cause some cardiac damage, in addition to that caused by ischaemia. Therefore, it is reasonable to attempt to increase the benefit obtainable with reperfusion by modulating inflammatory processes triggered by reperfusion itself. In this field, different potential therapeutic targets have been identified and interventions have been tested over the last 30 years. With the exception of adenosine, which probably does not act merely through inhibition of the inflammatory response, no other compounds have yet proven successful in clinical trials. Active research is ongoing. Broadening the approach from the heart to the cardiovascular system, promising data is emerging on cardiovascular protection conferred by statins in patients with coronary heart disease (CHD) and high levels of C-reactive protein (CRP), a systemic marker of inflammation. Similarly, results of trials aimed at preventing cardiovascular events by eradicating chronic infections will be among the first to directly test whether such therapies will decrease risks of cardiovascular disease.
Latini
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R
Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche "Mario Negri," Milano, Italy. latini@marionegri.it
Masson
S
S
Bertini
R
R
Maggioni
A P
AP
Ghezzi
P
P
Calvillo
L
L
D000241:Adenosine / Q000627:therapeutic use; D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003165:Complement System Proteins / Q000627:therapeutic use; D016207:Cytokines / Q000502:physiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006331:Heart Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D061965:Matrix Metalloproteinase Inhibitors; D009504:Neutrophils / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
D002317:Cardiovascular Agents; D016207:Cytokines; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D017382:Reactive Oxygen Species; D003165:Complement System Proteins; D000241:Adenosine