JSM atherosclerosis最新文献

Hypertriglyceridemia (HTG) is an independent factor of atherosclerotic cardiovascular disease and a hallmark of many metabolic disorders. However, the molecular etiology of HTG is still largely unknown. In mice, severe HTG may be induced by expression of specific mutants of apolipoprotein (apo) A-I or wild type (WT) apoE4. Expression of a certain apoE4 mutant results in mild HTG, while expression of another apoE4 mutant or WT apoA-I results in normal plasma triglyceride (TG) levels. Biophysical studies of the apoA-I and apoE4 forms associated with HTG help better understand the molecular mechanisms of induction of HTG by these proteins. The studies show that the apoA-I and apoE4 forms that induce HTG have a destabilized and more loosely folded conformation in solution than their counterparts not associated with HTG. Disruption of the protein salt bridge networks by the mutations is likely responsible for the observed structural changes. Each apoA-I and apoE4 form that induced HTG show enhanced binding to model TG-rich particles. HTG appeared to positively correlate with the apolipoprotein ability to bind to TG-rich particles. This implies that in vivo, the conformational changes in the apolipoproteins that induce HTG facilitate their binding to plasma TG-rich lipoproteins. We discuss metabolic pathways leading to the development of HTG that may result from enhanced binding of the apolipoproteins to TG-rich lipoproteins in circulation. While various factors may be involved in the development of HTG in humans, it is possible that structural alterations that increase affinity of apolipoproteins to TG-rich lipoproteins may contribute to some cases of this disorder.

Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi. T. cruzi targets adipose tissue, which serves as a reservoir of this parasite. T. cruzi infection of adipose tissue is characterized by increased lipolysis, oxidative stress, and parasitemia. High fat diet (HFD) decreases lipolysis and increases the survival rate in the mice infected with T. cruzi during acute infection. However, the effect of HFD on oxidative stress in adipose tissue has not been examined in detail. In the present study we evaluated the effect of HFD on oxidative stress markers in both white and brown adipose tissues (WAT and BAT) during acute infection. We used qPCR to examine the mRNA expression levels of genes involved in several antioxidant defence systems, such as those acting in ROS metabolism, peroxidases, and relevant oxygen transporter genes. The result of our study showed that HFD regulates the expression levels of oxidative stress genes in adipose tissues and that these effects are often different in WAT and BAT. For instance, while HFD down-regulated the levels of most antioxidant genes in both WAT and BAT, it differentially affected the expression pattern of genes involved in ROS metabolism (e.g. peroxidases) in WAT and BAT tissues of infected mice. Together with our previous studies, these findings show that infection and diet both regulate antioxidant enzymes and other oxidative stress defenses in mouse adipose tissues during acute T. cruzi infection.

The renin-angiotensin system (RAS) has long been known as a regulator of blood pressure and fluid homeostasis. In past several decades, local renin-angiotensin systems have been discovered in various tissues and novel actions of angiotensin II (ANGII) have emerged as an immunomodulator and profibrotic molecule. The enzyme responsible for its synthesis, angiotensin-converting-enzyme (ACE), is present in high concentrations in lung tissue. ACE cleaves angiotensin I (ANG I) to generate angiotensin II (ANGII), whereas ACE2 inactivates ANGII and is a negative regulator of the system. The RAS has been implicated in the pathogenesis of pulmonary hypertension, acute lung injury and experimental lung fibrosis. Recent studies in animal and humans indicate that the RAS also plays a critical role in fetal and neonatal lung diseases. Further investigations are needed to better understand the role of RAS, ACE and ACE-2 in neonatal lung injury. With more clarity and understanding, the RAS and/or ACE-2 may ultimately prove to constitute potential therapeutic targets for the treatment of neonatal lung diseases. This manuscript reviews the evidence supporting a role for RAS in neonatal lung injury and discusses new possibilities for therapeutic approaches.