The Indonesian Biomedical Journal

17-32

Authors: Anna Meiliana, Andi Wijaya

BACKGROUND: The strong inverse association of plasma levels of high-density lipoprotein (HDL) cholesterol with coronary heart disease (CHD) found in human epidemiological studies led to the development of the ‘HDL cholesterol hypothesis’, which posits that intervention to raise HDL cholesterol will result in reduced risk of CHD. A number of recent developments have brought the potential protective role of HDL into question. Several clinical trials of agents that substantially raise HDL-C have been demonstrated to not reduce CHD event rates. CONTENT: For decades, HDL and HDL-cholesterol (HDL-C) levels were viewed as synonymous, and modulation of HDL-C levels by drug therapy held great promise for the prevention and treatment of cardiovascular disease. Nevertheless, recent failures of drugs that raise HDL-C to reduce cardiovascular risk and the now greater understanding of the complexity of HDL composition and biology have prompted researchers in the field to redefine HDL. As such, the focus of HDL has now started to shift away from a cholesterol-centric view toward HDL particle number, subclasses, and other alternative metrics of HDL. Many of the recently discovered functions of HDL are, in fact, not strictly conferred by its ability to promote cholesterol flux but by the other molecules it transports, including a diverse set of proteins, small RNAs, hormones, carotenoids, vitamins, and bioactive lipids. Based on HDL’s ability to interact with almost all cells and deliver fat-soluble cargo, HDL has the remarkable capacity to affect a wide variety of endocrine-like systems. SUMMARY: There is a significant need to redefine HDL and its benefit. HDL transports a diverse set of functional proteins, including many binding proteins. HDL transports and deliver vitamins, carotenoids, and other small molecules. Moreover, HDL transports hormones, steroids and bile acids, and can modulate multiple endocrine pathways. HDLs also transport and deliver microRNAs to recipient cells and control gene expression. Likewise, HDLs carry bioactive lipids and can activate signaling cascades and receptors that control endothelial apoptosis, migration, survival and activation. Many of HDL’s alternative noncholesterol cargo likely confer many of HDL’s alternative functions.

45-50

Authors: Rusli Muljadi, Bachtiar Murtala, Peter Kabo, FX Budhianto Suhadi

BACKGROUND: Cardiovascular disease is one of the atherosclerosis etiologies that can lead to death. Diabetes mellitus increases the risk of atherosclerosis. Screening tool is very beneficial for detecting atherosclerotic plaque, especially in subclinical atherosclerotic cases. Carotid intima-media thickness (CIMT) and coronary artery calcification score (CACS) are two kinds of tools that are widely used, and each of these tools has its own superiority. This study was aimed to investigate the sensitivity and specificity of both of these tools as screening tools. METHODS: The study was conducted with a cross sectional design involving 43 diabetic and 68 non-diabetic male subjects aged above 45 years old. All subjects fulfilled inclusion criteria. Carotid artery ultrasonography and CACS measurement were performed. RESULTS: Fischer exact test was used to show a significant correlation between CIMT and CACS (p<0.05). Diagnostic test was used to assess the sensitivity of CIMT toward CACS in above 75 percentile. The left common carotid artery (LCCA) showed the highest sensitivity either in diabetic (76.4%) or non-diabetic male subjects (90%). CONCLUSION: CIMT has the same sensitivity with CACS. CIMT can be used as the preferred screening tool for high risk patients and as a substitution tool to CACS for low risk patients in subclinical atherosclerosis detection.

57-62

Authors: Ferry Sandra, Janti Sudiono, Elina Ardiani Sidharta, Elisabeth Pricilia Sunata, Dea Jane Sungkono, Yanni Dirgantara, Angliana Chouw

BACKGROUND: Secreted factors contained in conditioned media (CM) of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) known as secretome, was suspected to have important roles in regulating cells. This study was conducted to investigate the role of CM-hUCB-MSCs-derived secretome in apoptosis and growth of HeLa cells. METHODS: HeLa cells were treated with secretome in various concentrations (0, 0.2, 2 and 20%) for 24 and 48 hours. Trypan blue exclusion assay was performed to detect cell viability. Meanwhile sub-G1 apoptotic assay was performed to detect apoptotic cells. The transition of mitochondrial transmembrane potential (TMP), which occurs in the apoptotic process, was analyzed by mitochondrial membrane potential (ΔΨM) assay. Both sub-G1 and ΔΨM assays were performed using FACSCanto flow cytometer. Statistical analyses were conducted using IBM SPSS Statistics to detect significance level at p<0.05. RESULTS: Secretome significantly induced cell death starting at concentration of 0.2% within a 24-hour period (p<0.05). Secretome significantly induced cell death in concentration and time dependent manner (p<0.05). The cell death was then confirmed as apoptosis through sub-G1 analysis. Due to the underlying apoptotic mechanism, we found distinct decrease of TMP, indicating an increase in mitochondrial membrane permeability of HeLa cells. In addition, we found that HeLa cell growth was inhibited partially by secretome. CONCLUSION: Taken together, we conclude that CMhUCB-MSCs-derived secretome significantly induced apoptosis of HeLa cells in a concentration and time dependent manner through mitochondrial apoptotic pathway. The secretome might also play important role in inhibiting HeLa cell growth.