Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a recently identified and potentially useful plasma biomarker for cardiovascular and atherosclerotic diseases. However, the correlation between the Lp-PLA₂ activity and carotid atherosclerosis remains poorly investigated in patients with metabolic syndrome (MetS). The present study aimed to evaluate the potential role of Lp-PLA₂ as a comprehensive marker of metabolic syndrome in individuals with and without carotid atherosclerosis. We documented 118 consecutive patients with MetS and 70 age- and sex-matched healthy subjects served as controls. The patients were further divided into two groups: 39 with carotid plaques and 79 without carotid plaques to elucidate the influence of Lp-PLA₂ on carotid atherosclerosis. The plasma Lp-PLA₂ activity was measured by using ELISA method and carotid intimal-media thickness (IMT) was performed by ultrasound in all participants. Lp-PLA₂ activity was significantly increased in MetS subgroups when compared with controls, and was higher in patients with carotid plaques than those without plaques (P < 0.05). Furthermore, we found that significant difference in Lp-PLA₂ was obtained between patients with three and four disorders of metabolic syndrome (P < 0.01). Age (β = 0.183, P = 0.029), LDL-cholesterol (β = 0.401, P = 0.000) and waist-hip ratio (β = 0.410, P = 0.000) emerged as significant and independent determinants of Lp-PLA₂ activity. Multiple stepwise regression analysis revealed that LDL-cholesterol (β = 0.309, P = 0.000), systolic blood pressure (β = 0.322, P = 0.002) and age (β = 0.235, P = 0.007) significantly correlated with max IMT, and Lp-PLA₂ was not an independent predictor for carotid IMT. Lp-PLA₂ may be a modulating factor for carotid IMT via age and LDL-cholesterol, not independent predictor in the pathophysiological process of carotid atherosclerosis in patients with MetS.

Saxagliptin (SAX) can protect against tissue damage caused by diabetic nephropathy. However, whether this compound can restore kidney function, and its specific mechanism of action remain unclear. The present study explored the therapeutic effects and mechanisms of SAX. Male Wistar rats (8 weeks old) were randomly divided into the following groups: A control group (n=10); a group with streptozocin‑induced diabetes mellitus (DM) treated with saline (n=20); and a group with streptozocin‑induced DM treated with SAX (n=20). Following 20 weeks of treatment, renal function and the extent of renal damage were assessed based on histological staining using hematoxylin and eosin, periodic acid‑Schiff and Masson's trichrome staining. The experimental results indicated that Streptozocin induction of DM led to thicker basement membranes in mesangial cells and a more abundant extracellular matrix. These changes were ameliorated following treatment with SAX. The data demonstrated that renal tissue and renal cell apoptosis were ameliorated significantly following treatment with SAX. Furthermore, the expression levels of the apoptotic genes poly (ADP‑ribose) polymerase‑1 (PARP‑1) and caspase 3 were significantly decreased following treatment with SAX. Therefore, SAX may reduce the extent of renal apoptosis and pathological outcomes in diabetic nephropathy by downregulating the expression of caspase 3 and PARP‑1 in the death receptor pathway of apoptosis.

Sacubitril/valsartan (S/V) has been shown to be an effective antihypertensive drug combination. However, its therapeutic effects on blood pressure (BP) and hemodynamics as well as left ventricular (LV) remodeling in resistant hypertension (RHTN) remain unclear. Eighty-six patients completed this self-control study, during which olmesartan was administered within the first 8 weeks (phase 1) followed by S/V within the second 8 weeks (phase 2), with nifedipine and hydrochlorothiazide taken as background medications. Office BP, echocardiography and hemodynamics assessment using impedance cardiography were performed at baseline, the eighth and sixteenth weeks. The reduction in office BP was larger in phase 2 than in phase 1 (19.59/11.66 mmHg vs. 2.88/1.15 mmHg). Besides, the treatment in phase 2 provided greater reductions in systemic vascular resistance index (SVRI) and thoracic blood saturation ratio (TBR), with differences between two phases of -226.59 (-1212.80 to 509.55) dyn·s/cm⁵/m² and -0.02 (-0.04 to 0.02). Switching from olmesartan to S/V also significantly reduced E/E`, LV mass index, LV end-diastolic volume index and LV end-systolic volume index (all P < 0.05). Decreases in AS, SVRI and TBR were correlated with changes in indicators of LV remodeling (all P < 0.05). And the correlation still remained even after adjusting for confounders including changes in BP. Switching from olmesartan to S/V effectively lowered BP and reversed ventricular remodeling in RHTN. In addition, hemodynamics improvement was also observed. Changes in hemodynamics played an important role in reversing LV remodeling of S/V, which were independent of its antihypertensive effect.