Effects of cilostazol on serum lipoprotein concentrations and particle size of low-density lipoproteins in patients with dyslipidemic NIDDM

Intermittent claudication (IC) is one of the most frequent forms of lower extremity peripheral arterial disease (PAD) and is most commonly caused by arterial atherosclerosis. Its clinical manifestation includes fatigue, discomfort, or pain occurring in limb muscles due to exercise-induced ischemia, thus limiting the ability of IC patients to walk and exercise. In addition to lifestyle changes (diet, exercise, and smoking cessation), pharmacological treatments are needed. Pathologically, atherosclerotic lesions cause a mismatch in oxygen supply and metabolic demand in the leg muscles during walking/exercise. This subjects the muscles to repeated ischemia and reperfusion injury that can alter structure and oxidative metabolism, resulting in insufficient utilization of oxygen supply. Despite extensive research efforts, cilostazol and pentoxifylline are the only drugs indicated for relieving the symptoms of IC, with cilostazol demonstrating significant improvement in walking distance and quality of life in these patients. Originally developed as a PDE3 inhibitor, cilostazol was later found to have several other pharmacological actions, and its success has been attributed to its multifactorial actions on platelets, endothelium, smooth muscle, and lipid profiles. Using cilostazol as an example, we discuss the rationales and pitfalls of targeting PDEs in IC, and potential strategies for the development of new and more effective pharmacological treatments.

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Phosphodiesterases as Targets for Intermittent Claudication

Liu

Shakur

Kambayashi

2011

Phosphodiesterases as Drug Targets

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Bench to Bedside

Kambayashi¹,

Shakur²,

Liu³

2006

Cyclic Nucleotide Phosphodiesterases in Health and Disease

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Effects of cilostazol on serum lipoprotein concentrations and particle size of low-density lipoproteins in patients with dyslipidemic NIDDM

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Phosphodiesterases as Targets for Intermittent Claudication

Phosphodiesterases as Targets for Intermittent Claudication

Bench to Bedside

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