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

Administration of SPLA2 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 SPLA2 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 sPLA2 inhibitors. Significantly, administration of SPLA2 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 sPLA2 inhibitors and statins resulted in a synergistic decrease in plaque content. Therefore, also provided herein are compositions comprising one or more SPLA2 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.