Background— The proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes independently of its enzymatic activity the degradation of the low-density lipoprotein (LDL) receptor. PCSK9 gain of function in humans leads to autosomal dominant hypercholesterolemia, whereas the absence of functional PCSK9 results in ≈7-fold lower levels of LDL cholesterol. This suggests that lowering PCSK9 may protect against atherosclerosis. Methods and Results— We investigated the role of PCSK9 in atherosclerosis in C57BL/6 wild-type (WT), apolipoprotein E–deficient, and LDL receptor–deficient mouse models. Circulating cholesterol levels, fast protein liquid chromatography profiles, aortic cholesteryl esters (CE), and plaque sizes were determined. Intima-media thicknesses were measured by ultrasound biomicroscopy. First, mice expressing null (knockout [KO]), normal (WT), or high (transgenic [Tg]) levels of PCSK9 … arabic 12 English 86
Maxime Denis, Ahmed Zaid(1-2012)

Abstract: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipid metabolism, associated with elevated levels of low-density lipoprotein-cholesterol (LDLC), which can lead to premature cardiovascular disease and early death. Early diagnosis and initiation of treatment is important to prevent morbidity and mortality. Autosomal dominant hypercholesterolemia (ADH) is largely due to mutations in the low-density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), or the proprotein convertase subtilisin/kexin type 9 (PCSK9). In this study, genomic DNA of unrelated Libyan individuals with clinically diagnosed (FH) was analyzed by direct sequencing after dependent specific PCR primers amplification and DNA purification. That led to the identification of PCSK9 gene mutations for the first time in Libyan population which was compare to other populations. All 12 exons of PCSK9 gene and boundaries genotyped polymorphisms were sequenced, including leucine repeats coded in exon 1, by fluorescently tagged markers. We identified an allele for the rs67610340 polymorphism: an in-frame deletion, c.61_63delCTG (L8). We also identified another allele rs67610340 polymorphism: an in frame insertion c.61_63InsCTG (L10). The insertion and deletion alleles were both in exon 1 and could be associated with a risk and severity of coronary artery disease (CAD), suggesting a direct effect of PCSK9 on atherogenesis. arabic 11 English 90
Ghada Salem, Ahmed Zaid(1-2017)

Bisphenol A (BPA), an endocrine and metabolic disruptor, is widely used to manufacture polycarbonate plastics and epoxy resins. Accumulating evidence suggests that paternal BPA exposure adversely affects male germlines and results in atypical reproductive phenotypes that might persist for generations to come. Our study investigated this exposure on testicular architecture and sperm quality in mouse offspring, and characterised underlying molecular mechanism(s). A total of 18 immature male Swiss albino mice (3.5 weeks old) were randomly divided into three groups and treated as follows: Group I, no treatment (sham control); Group II, sterile corn oil only (vehicle control); Group III, BPA (400 μg/kg) in sterile corn oil. At 9.5 weeks old, F0 males were mated with unexposed females. F0 offspring (F1 generation) were monitored for postnatal development for 10 weeks. At 11.5 weeks old, the animals were sacrificed to examine testicular architecture, sperm parameters, including DNA integrity, and oxidative stress biomarkers (malondialdehyde (MDA), protein carbonylation (PC), and nitric oxide (NO)). Results showed that BPA significantly induced changes in the body and testis weights of the F0 and F1 generation BPA lineages compared to F0 and F1 generation control lineages. A decrease in sperm count and motility with further, increased sperm abnormalities, no or few sperm DNA alterations and elevated levels of MDA, PC, and NO were recorded. Similar effects were found in BPA exposed F0 males, but were more pronounced in the F0 offspring. In addition, BPA caused alterations in the testicular architecture. These pathological changes extended transgenerationally to F1 generation males’ mice, but the pathological changes were more pronounced in the F1 generation. Our findings demonstrate that the biological and health BPA impacts do not end in paternal adults, but are passed on to offspring generations. Hence, the linkage of seen testis and sperm pathologies in the F1 generation to BPA exposure of their parental line was evident in this work. The findings also illustrate that oxidative stress appears to be a molecular component of the testis and sperm pathologies. arabic 18 English 101
Mohamed A. Al-Griw(11-2020)