Recent developments in the effects of nitric oxide-donating statins on cardiovascular disease through regulation of tetrahydrobiopterin and nitric oxide.

Since the discovery of the importance of nitric oxide (NO) to the human body three decades ago, numerous laboratory and clinical studies have been done to explore its potential therapeutic actions on many organs. In the cardiovascular system, NO works as a volatile signaling molecule regulating the vascular permeability and vascular tone, preventing thrombosis and inflammation, as well as inhibiting the smooth muscle hyperplasia. Thus, NO is important in the prevention and treatment of cardiovascular disease. NO is synthesized by NO synthase (NOS) with tetrahydrobiopterin (BH4) as the crucial cofactor. Many studies have been done to form nitric oxide donors so as to deliver NO directly to the vessel walls. In addition, NO moieties have been incorporated into existing therapeutic agents to enhance the NO bioavailability, including statins. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA), the rate-limiting enzyme of the mevalonate pathway. By inhibiting this pathway, statins lower blood cholesterol and exert their pleiotropic effects through activity in reaction cascades, such as Rho/ROCK and Rac 1/NADPH oxidase pathways. Statins have also been observed to implement their non-lipid effects by promoting BH4 synthesis with increase of NO bioavailability. Furthermore, NO-donating statins in laboratory studies have demonstrated to produce better therapeutic effects than their parent's drugs. They offer better anti-inflammatory, anti-proliferative and antithrombotic actions on cardiovascular system. They also cause better revascularization in peripheral ischemia and produce greater enhancement in limb reperfusion and salvage. In addition, it has been shown that NO-donating statin caused less myotoxicity, the most common side effect related to treatment with statins. The initial studies have demonstrated the superior therapeutic effects of NO-donating statins while producing fewer side effects.

Recent development in the effects of statins on cardiovascular disease through Rac1 and NADPH oxidase.

Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), are important lipid-lowering agents. After two decades of laboratory and clinical studies, their pleiotropic effects appear well-established. One of these effects is through the regulation of Rac1 and NADPH oxidases. Relatively few human trials have been carried out with regards to the action of statins on Rac1 and NADPH oxidases, but similar positive effects were also observed in blood vessels and myocardium of participants in the trials. Besides, more specific biomarkers for the antioxidation effects of statins have been developed in the recent two years; both monitoring of the progress of disease and the effects of medical therapy will be possible. Further development of the potency and specificity of statin may enhance their therapeutic potential on cardiovascular disease.

The role of surfactant in respiratory distress syndrome.

The key feature of respiratory distress syndrome (RDS) is the insufficient production of surfactant in the lungs of preterm infants. As a result, researchers have looked into the possibility of surfactant replacement therapy as a means of preventing and treating RDS. We sought to identify the role of surfactant in the prevention and management of RDS, comparing the various types, doses, and modes of administration, and the recent development. A PubMed search was carried out up to March 2012 using phrases: surfactant, respiratory distress syndrome, protein-containing surfactant, protein-free surfactant, natural surfactant, animal-derived surfactant, synthetic surfactant, lucinactant, surfaxin, surfactant protein-B, surfactant protein-C.Natural, or animal-derived, surfactant is currently the surfactant of choice in comparison to protein-free synthetic surfactant. However, it is hoped that the development of protein-containing synthetic surfactant, such as lucinactant, will rival the efficacy of natural surfactants, but without the risks of their possible side effects. Administration techniques have also been developed with nasal continuous positive airway pressure (nCPAP) and selective surfactant administration now recommended; multiple surfactant doses have also reported better outcomes. An aerosolised form of surfactant is being trialled in the hope that surfactant can be administered in a non-invasive way. Overall, the advancement, concerning the structure of surfactant and its mode of administration, offers an encouraging future in the management of RDS.

Recent development in pleiotropic effects of statins on cardiovascular disease through regulation of transforming growth factor-beta superfamily.

BACKGROUND: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are a drug class that reduce the level of cholesterol in the blood. As a result, statins are used to suppress the progression of cardiovascular disease. Evidence points to another component of statins involving the non-lipid effects of the drug class in preventing cardiovascular disease. One specific mediator of this action is the transforming growth factor ß (TGF-ß) superfamily. The TGF-ß superfamily consists of proteins that include TGF-ß and bone morphogenetic proteins (BMPs). These proteins regulate cellular pathways to mediate effects including immunomodulation, cell cycling, and angiogenesis. One pathway that mediates these effects is Ras. Moreover, within this pathway, different functions are possible depending on the activation of the specific receptor subtype. This review discusses the recent development of the non-lipid effects of statins in preventing cardiovascular disease progression by regulating Ras pathway of the TGF-ß superfamily, especially RhoA/ROCK pathway. METHODS: A systematic PubMed database search of all English-language articles up to 2011 was conducted using the following terms: statin, TGF-ß, Ras, ROCK, GGPP, inducible nitric oxide synthase, endothelial nitric oxide synthase, actin filament formation, PPARγ, MMP-2, and human trials. CONCLUSION: With better understanding of the pathway, various mediators were identified; some of these mediators are important biomarkers producing more specific and accurate assessment of the pleiotropic effects of statins. The review of human trials also highlights that more specific biomarkers are employed in recent studies, and the non-lipid effects on human subjects are more accurately documented. Confirmation of the accuracy of these biomarkers by further large-scale studies and further development of new biomarkers may prove an important path leading to better patient selection for treatment, and thus better cost-effectiveness may be achieved.