Cardiovascular Therapeutics - Applications of Biotechnology in Cardiovascular Therapeutics - page 24

lesion formation was also studied in a mouse model of atherosclerosis. Lipid
profiles were unaffected, but the area of atherosclerotic lesion and plaque necrosis
were significantly reduced following 8 weeks of nicorandil treatment in ApoE-
deficient mice fed an atherogenic diet. Nicorandil significantly reduced the expres-
sion levels of endoplasmic reticulum stress biomarkers, C/EBP homologous protein
(CHOP) and glucose regulated protein/BiP in atherosclerotic lesions. Nicorandil
significantly attenuated tunicamycin-induced CHOP upregulation in cultured
THP-1 macrophages. The conclusion from these studies was that nicorandil exerts
its anti-atherogenic effect by mechanisms different from those of statins. Long-term
nicorandil treatment can be considered as a second-line prevention therapy for
patients with coronary artery disease.
Statins for Cardioprotection in Dilated Cardiac Myopathy
Statins are generally used for lowering cholesterol and indirectly protect against
coronary heart disease due to hypercholesterolemia. Statins also have an immuno-
modulating effect in inflammatory processes affecting the heart. Dilated cardio-
myopathy (DCM) is a multifactorial disease in which there is enlargement and
systolic dysfunction of one or both ventricles leading to congestive heart failure
(CHF), which is a progressive disease with high morbidity and mortality, suggest-
ing that important pathogenic mechanisms are not modified by current symptom-
atic treatment. Inflammation plays a role in the development and progression of
CHF, influencing heart contractility and hypertrophy, promoting apoptosis, and
contributing to myocardial remodeling. Immunomodulating treatments, such as
statins, have shown promising results in patients with cardiomyopathies. Statins, by
inhibiting inflammation and reducing endothelial dysfunction, lead to the improve-
ment of left ventricular function and exercise tolerance in patients with DCM in
New York Heart Association class II or III and with normal or increased levels of
lipids (Bielecka-Dabrowa et al. 2011 ).
Role of Proteomics in Cardioprotection
Proteomics of Cardioprotective Role of Preconditioning
Combined proteomic and metabolomic analyses provide direct evidence of the
effect of protein expression on cellular processes, and this approach has been used
to investigate the cardioprotective mechanisms following exposure to nitrate, which
is an important bioactive molecule, capable of conferring cardioprotection and a
variety of other benefits in the cardiovascular system (Perlman et al. 2009 ). Nitrate
administration resulted in a short-lived increase in cardiac nitrate levels, but sub-
stantial elevations in cardiac ascorbate oxidation. This was accompanied by significant
improvements in cardiac contractile recovery following ischemia-reperfusion after