Lipoprotein-associated Phospholipase A2 and Coronary Heart Disease

Ruan

Evidence-Based Complementary and Alternative Medicine

2021

Acute heart failure (AHF) occurs mostly in the elderly, which is a syndrome that occurs in the later stages of the development of cardiovascular disease. Due to the sharp decline in the patient’s heart function, the patient has a high mortality rate and a poor prognosis, which seriously threaten the life safety of the elderly. Therefore, early diagnosis of AHF and timely treatment are extremely important. Lipoprotein-associated phospholipase A2 (LP-PLA2) is a newly discovered cardiovascular-specific inflammatory marker, which is closely related to the formation and progression of atherosclerotic plaque and the occurrence and development of coronary heart disease. Soluble growth stimulation expression gene 2 (sST2) protein is a protein produced under the induction of mechanical stress in cardiomyocytes. It can act as a decoy receptor to mediate the interleukin-33 (IL-33)/ST2 signaling pathway to bind to IL-33, thereby reducing the myocardial protective effect and leading to myocardial remodeling. The purpose of this study was to explore the serum LP-PLA2 and sST2 levels in AHF patients and to analyze their correlation with the disease and their prognostic value. The results showed that the levels of serum LP-PLA2 and sST2 were increased in AHF patients, and the levels of serum LP-PLA2 and sST2 in patients with adverse prognostic events were higher than those in patients without adverse prognostic events. The levels of serum LP-PLA2 and sST2 are closely related to the degree of patients’ illness, among which the combined prediction of AHF patients with LP-PLA2 and sST2 has the highest value, which is worthy of promotion.

Section: Discussionmentioning

confidence: 99%

Correlation between Serum LP-PLA2 and sST2 Levels and the Condition of Patients with Acute Heart Failure and Their Prognostic Value

Ruan

Evidence-Based Complementary and Alternative Medicine

2021

Cardiovascular Research

“…Extracellular PLA2 is transported in association with lipoproteins (LP-PLA2), mainly LDL and Lp(a). 131 LP-PLA2 is a cardiovascular risk biomarker, 132 but clinical trials of PLA2 inhibitors did not reveal a positive impact on CVD. 133 However, specific effects on calcifications were not explored in those studies.…”

Section: Sources Of Phosphatementioning

confidence: 99%

From organic and inorganic phosphates to valvular and vascular calcifications

Bäck

Michel

2021

Calcification of the arterial wall and valves is an important part of the pathophysiological process of peripheral and coronary atherosclerosis, aortic stenosis, aging, diabetes, and chronic kidney disease. This review aims to better understand how extracellular phosphates and their ability to be retained as calcium phosphates on the extracellular matrix initiate the mineralization process of arteries and valves. In this context, the physiological process of bone mineralization remains a human model for pathological soft tissue mineralization. Soluble (ionized) calcium precipitation occurs on extracellular phosphates; either with inorganic or on exposed organic phosphates. Organic phosphates are classified as either structural (phospholipids, nucleic acids) or energetic (corresponding to phosphoryl transfer activities). Extracellular phosphates promote a phenotypic shift in vascular smooth muscle and valvular interstitial cells towards an osteoblast gene expression pattern, which provokes the active phase of mineralization. A line of defense systems protects arterial and valvular tissue calcifications. Given the major roles of phosphate in soft tissue calcification, phosphate mimetics and/or prevention of phosphate dissipation represent novel potential therapeutic approaches for arterial and valvular calcification.

Medicinal Research Reviews

“…In the past decade, a number of reviews have been published with respect to the structure, genetic aspects, biological roles, disease implications, and specific inhibitors of Lp‐PLA2 . In addition, Lp‐PLA2 has been reviewed as a part of the PLA2 superfamily or PAF‐AHs .…”

Section: Introductionmentioning

confidence: 99%

Lipoprotein‐associated phospholipase A2: The story continues

Huang

Wang

Shen

2019

125

140

Inflammation is thought to play an important role in the pathogenesis of vascular diseases. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation‐related diseases, mainly atherosclerosis. Although darapladib, the most advanced Lp‐PLA2 inhibitor, failed to meet the primary endpoints of two large phase III trials in atherosclerosis patients cotreated with standard medical care, the research on Lp‐PLA2 has not been terminated. Novel pathogenic, epidemiologic, genetic, and crystallographic studies regarding Lp‐PLA2 have been reported recently, while novel inhibitors were identified through a fragment‐based lead discovery strategy. More strikingly, recent clinical and preclinical studies revealed that Lp‐PLA2 inhibition showed promising therapeutic effects in diabetic macular edema and Alzheimer's disease. In this review, we not only summarized the knowledge of Lp‐PLA2 established in the past decades but also emphasized new findings in recent years. We hope this review could be valuable for helping researchers acquire a much deeper insight into the nature of Lp‐PLA2, identify more potent and selective Lp‐PLA2 inhibitors, and discover the potential indications of Lp‐PLA2 inhibitors.