Antisense Oligonucleotides to PAM mRNA as Potential Agents for Therapeutic Intervention in Cardiovascular Diseases

Polish - Japan Issue

Thrombolytic therapy provides clinical benefit in patients with vascular occlusions, dependingupon the organ or limb that is threated. The impact of therapeutic intervention varies from thequiet alteration of the course of deep vein thrombosis, for which non-life threatening postphlebitic syndrome can largely be avoided, to the striking reversal of pulmonary hypertensionand possible life-saving benefit in massive pulmonary embolism, the immediate alteration ofclinical course in acute peripheral arterial occlusion by reducing the need for surgical intervention, cardiopulmonary complication and one year mortality, and finally to the dramatic andlife-saving potential when applied in patients with acute myocardial infarction. At least threealternative and complementary approaches to improve thrombolytic therapy can be distinguished:a) earlier and accelerated treatment in order to reduce the duration of ischemia, b) developmentof alterative or engineered plasminogen activators with increased thrombolytic potency and/orspecific thrombolytic activity, in order to enhance coronary thrombolysis, and c) the use of morespecific and potent anticoagulant and antiplatelet agents for conjunctive use with thrombolyticagents, with the aim to accelerate recanalization and prevent reocclusion. In this report wediscuss the possibility of using antisense oligonucleotides specific to PAJ-l mRNA to reversiblydecrease PAI-1 level in blood plasma and thus prolong a half-life time of endogenous plasminogenactivators in circulation.

Zeszyt specjalny. Polish - Japan Issue