Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Enhance Angiogenesis in Diabetic Rats with Peripheral Artery Disease.

Background: Lower limb peripheral artery disease (PAD) is the main risk of diabetes mellitus which result to high mortality rate. Approximately, 50% of patients who receive several treatments have passed away or lost limbs at a year's follow-up. Secretome of hypoxia mesenchymal stem cells (S-MSCs) contains several active soluble molecules from hypoxia MSCs (H-MSCs) that capable inducing anti-inflammatory and vascular regeneration in PAD. Objective: In this study, we investigated the therapeutic potential of S-MSCs in improving dynamic function and angiogenesis of PAD diabetic rats. Methods: The PAD was established by the incision from the groin to the inner thigh and distal ligation of femoral arteries in rats with diabetes. Rats were administered with 200 µL and 400 µL S-MSCs that successfully filtrated using tangential flow filtration (TFF) system based on various molecular weight cut-off categories intravenously. ELISA assay was used to analyze the cytokines and growth factors contained in S-MSCs. Tarlov score were examined at day 1, 3, 5, 7, 10 and 14. The rats were sacrificed at day 14 and muscle tissues were collected for immunohistochemistry (IHC) and gene expression analysis. Results: ELISA assay showed that S-MSCs provides abundant level of VEGF, PDGF, bFGF, IL-10 and TGFß. In vivo administration of S-MSCs remarkably enhanced the Tarlov score. S-MSCs improved angiogenesis through enhancing VEGF gene expression and significantly increasing CD31 positive area in muscle tissue of PAD diabetic rats. Conclusion: Our findings suggest that S-MSCs could improves dynamic function and angiogenesis in PAD diabetic rats.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) as a marker of coronary lesion severity in stable coronary artery disease (CAD) patients.

Coronary artery disease (CAD) remains a significant global health concern with considerable high morbidity and mortality and its development is influenced by various genetic and environmental factors. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a vital regulator of low-density lipoprotein receptor (LDLR) metabolism, directly impacting serum cholesterol levels. However, its role in development of CAD is not fully understood. The aim of this study was to assess the association between the level of PCSK9 and coronary lesion severity in patients with CAD. A case-control study using consecutive sampling was conducted among CAD patients at H. Adam Malik General Hospital and Murni Teguh Memorial Hospital, Medan, Indonesia. A total of 200 CAD patients were divided into two groups based on the SYNTAX score: control (score ≤22, n=100) and case (score >22, n=100). Plasma PCSK9 levels were measured from venous blood using quantitative sandwich enzyme immunoassay. The Chi-squared test was used to analyze the data. Our data suggested that PCSK9 level was associated with coronary lesion severity (p<0.001) of which high PCSK9 level was associated with severe coronary lesion. We also found that hypertension (p<0.001), smoking (p=0.072), diabetes (p<0.001), dyslipidemia (p<0.001), obesity (p=0.023), and family history (p=0.001) were associated with lesion severity. Using the receiver operating characteristic (ROC) curve analysis, the cut-off 70.35 ng/mL of PCSK9 had sensitivity 75% and specificity 78% to predict severe coronary lesion. This study highlights that PCSK9 level has moderate sensitivity and specificity to predict the coronary lesion severity among CAD patients.

The effect of bay leaf extract (Syzygium polyanthum) on vascular endothelial growth factor (VEGF) and CD31 (PECAM-1) expression in acute coronary syndrome.

Aim To investigate effect of bay leaf extract in endothelial integrity, observed by vascular endothelial growth factor (VEGF) level, VEGF and CD31 expression. Methods Thirty-two acute coronary syndrome surgery-induced Wistar Rats (Rattus novergicus) were divided into 16 bay leaf extract (treatment) groups and 16 control groups, sacrificed on day 1, 4, 7, and 14 after the induction. Serum VEGF level was determined by ELISA and expression of VEGFR-2 and CD31 were detected on immunohistochemistry. Results This study showed increased expression of serum VEGF level, and VEGFR-2 expression was found significantly on day 7 and 14 in the treatment group compared to the control group. CD31 expression was significantly different compared to the control groups on day 4, 7, and 14 of administration. Conclusion The potential effect of bay leaf extract on angiogenesis in acute coronary syndrome (ACS) as adjuvant for the treatment. Bay leaf extract has been shown to support angiogenesis and maintain endothelial integrity that leads to better prognosis for reperfusion on ischemic tissue.

Syzygium Polyanthum Reduced TNF-α and ADAM17 Protein Expression in Myocardial Infarction Rat Model.

BACKGROUND: In myocardial infarction (MI), inflammatory cytokine including tumor necrosis factor-α (TNF-α) plays pivotal role throughout worsening processes and recovery, whereas its cleavage is controlled by a disintegrin and metalloproteinases-17 (ADAM-17). Syzygium polyanthum (Wight) is widely used plant in Indonesia and Southeast Asian countries to treat various illnesses. OBJECTIVE: This study aimed to analyze the effect of S. polyanthum extract towards TNF-α and ADAM17 expressions in MI rat model. METHODS: Myocardial infarction were surgically induced in wistar rats by ligating left anterior descending coronary artery in both treatment and control group. Around 3.6 mg of S. polyanthum extract (SPE) was administered via nasogastric tube to treatment groups, while control group received only saline. Serum TNF-α level and expression of TNF-α and ADAM17 in blanching heart muscle was examined in both groups on day 1, day 4, day 7, and day 14 after treatment with SPE. RESULTS: Reduction of serum TNF-α levels was markedly seen from day 4 in treatment group and was lower than in control group since day 4. Expression of ADAM17 was reduced and expression of TNF-α was only seen in myocardial membrane in group with SPE treatment. CONCLUSION: Syzygium polyanthum exerts its anti-inflammatory effect by decreasing ADAM17 expression subsequently lowering TNF-α regulation in MI rat model.

The effect of bay leaf extract Syzygium polyanthum (Wight) Walp. on C-reactive protein (CRP) and myeloperoxidase (MPO) level in the heart of rat model of myocardial infarction.

Aim To study the anti-inflammatory effect of bay leaf on C-reactive protein (CRP) and myeloperoxidase (MPO) level in the heart of rat model with myocardial infarction. Methods In the first phase, results of pathological examination and biochemical assay were compared between rats with and without induction of myocardial infarction. In the second phase, the effect of bay leaf extract on CRP and MPO of rats with myocardial infarction was studied. Results C-reactive protein and MPO were higher in rats which had myocardial infarction. Administration of bay leaf extract reduced levels of CRP and MPO in the rats started from day 4 after the induction of myocardial infarction. Conclusion Anti-inflammatory effect of bay leaf is confirmed, reflected by decreasing of CRP and MPO levels of rat model with myocardial infarction.