Project Grant R21HD114073

APELIN RECEPTOR AXIS AND LONG-TERM CONSEQUENCES OF PREECLAMPSIA - SUMMARY PREECLAMPSIA (PE) IS A HYPERTENSIVE DISORDER OF PREGNANCY THAT OCCURS IN 5-7% OF ALL PREGNANCIES. WOMEN EXPOSED TO PE ARE MORE LIKELY TO DEVELOP CARDIOVASCULAR AND SUBCLINICAL CEREBROVASCULAR EVENTS LATER IN LIFE. RECENT STUDIES SUGGEST AN ALARMING TREND THAT WOMEN WITH A HISTORY OF PE OFTEN EXPERIENCE PRONOUNCED SUBJECTIVE COGNITIVE AND PSYCHOLOGICAL DYSFUNCTION THAT SIGNIFICANTLY ALTERS THEIR QUALITY OF LIFE. ALTHOUGH THE EXACT MECHANISMS OF THIS SUBCLINICAL DISEASE ARE NOT WELL UNDERSTOOD, ENDOTHELIAL DYSFUNCTION AND INFLAMMATION ARE IMPLICATED IN THE PATHOGENESIS OF THE CEREBROVASCULAR AND COGNITIVE SYNDROME AFTER PE. THE APELINERGIC SYSTEM, CONSISTING OF APELIN, ELABELA (ELA), AND THE APELIN RECEPTOR (APJ), IS A NOVEL THERAPEUTIC PATHWAY IN PREECLAMPSIA. OUR STUDIES DEMONSTRATED THAT APELIN HAS ANTI-HYPERTENSIVE AND RENO-PROTECTIVE EFFECTS. HOWEVER, APELIN ALSO REDUCES BRAIN EDEMA, INFLAMMATION AND OXIDATIVE STRESS IN MODELS OF TRANSIENT MODEL OF FOCAL CEREBRAL ISCHEMIA, ISCHEMIA-REPERFUSION, AND STROKE SUGGESTING ITS POTENTIAL AS NEUROPROTECTOR. STUDIES PROPOSED IN THIS APPLICATION ARE BASED ON THE CLINICAL EVIDENCE SUGGESTING A LINK BETWEEN PREECLAMPSIA AND VASCULAR DEMENTIA- LIKE SYNDROME EXPERIENCED BY WOMEN YEARS AFTER THE EXPOSURE TO PE. OUR STUDIES WILL ESTABLISH THE NEUROPROTECTIVE ACTIONS OF APELINERGIC AXIS ON LONG-TERM CEREBROVASCULAR CONSEQUENCES OF PREECLAMPSIA. THE ESTABLISHED AND WELL-CHARACTERIZED MODELS OF NORMAL PREGNANCY AND PREECLAMPSIA ARE READILY AVAILABLE IN OUR LABORATORY AND WILL BE USED FOR THIS PROJECT. THESE STUDIES WILL IMPROVE OUR UNDERSTANDING OF THE PROTECTIVE ROLE OF APELIN/APJ AXIS IN PREECLAMPSIA.