CARDIOVASCULAR DISEASE TREATMENT AND DISLIPIDEMIA USING SECRETORY PHOSPHOLIPASE A2 INHIBITORS (SPLA2) AND SPLA2 INHIBITOR COMBINATION THERAPIES

摘要

Administration of SPLASUB2/SUB inhibitors has been found to decrease cholesterol levels, atherosclerotic plaque formation and aortic aneurysm in mice, and to decrease cholesterol and triglyceride levels in humans. Interestingly, administration of SPLASUB2/SUB inhibitors was found to decrease cholesterol levels even when the inhibitors were administered only once per day. Therefore, provided herein are methods of treating dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome, by administering one or more sPLASUB2/SUB inhibitors. Significantly, administration of SPLASUB2/SUB inhibitors and various compounds used in the treatment of CVD, such as for example statins, resulted in greater decreases in LDL and LDL particle levels in a synergistic manner. In addition, administration of sPLASUB2/SUB inhibitors and statins resulted in a synergistic decrease in plaque content. Therefore, also provided herein are compositions comprising one or more SPLASUB2/SUB inhibitors and one or more compounds used in the treatment of CVD, such as for example statins, and methods of using these compositions to treat dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome.