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Statins do more than just lower cholesterol

Insufficiency in coronary blood supply results in myocardial ischemia and consequently, various clinical syndromes and irreversible injuries. Myocardial damage occurs as a result of two processes during acute myocardial infarction (MI): ischemia and subsequent reperfusion. According to the available evidence, oxidative stress, excessive inflammation reaction, reactive oxygen species (ROS) generation, and apoptosis are crucial players in the pathogenesis of myocardial ischemia/reperfusion (IR) injury. There is emerging evidence that Janus tyrosine kinase 2 (JAK2) signal transducer and activator of the transcription 3 (STAT3) pathway offers cardioprotection against myocardial IR injury. This article reviews therapeutics that exert cardioprotective effects against myocardial IR injury through induction of JAK2/STAT3 pathway.

Previously, our group found that the dietary trace mineral element selenium and vitamin B₆ (VitB₆) alone was involved in lipid metabolism. However, the effects of selenium combined with VitB₆ on hyperlipidemia and lipid metabolism have not been reported until now. We hypothesized that selenium and VitB₆ cosupplementation would alleviate the hyperlipidemic and hepatic dysfunction and with minimum side effects in a Sprague-Dawley rat model of hyperlipidemia induced by a high-fat diet. Our results showed that selenium combined with VitB₆ could improve dyslipidemia and displayed better in vivo hypocholesterolemic abilities at early intervention. Moreover, cosupplementation reduced atherogenic indexes (atherogenic index and atherogenic index of plasm) and the ratio of ApoB/ApoA1. The liver function index aspartate aminotransferase in serum was reduced, as was and total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol in liver. The intervention also increased the levels of ApoA1 in serum and high-density lipoprotein cholesterol of liver. In addition, the combination of selenium and VitB₆ decreased liver lipid deposition and alleviated steatosis, reduced adipocyte size of white adipose tissue, increased the activities of hepatic lipase and total lipase and the hepatic 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) level, decreased the hepatic mRNA transcription of lipogenic and regulatory genes including Srebf1 and downstream fat synthesis-related enzymes (Acc and Fasn) and cholesterol synthesis speed limiting enzyme Hmgr, increased the mRNA abundance of Lcat and Cyp7a1, increased the protein expression of SIRT1 and PPARα, and up-regulated the protein expression of sterol regulatory element–binding protein 1c in the livers of hyperlipidemia rats. We first demonstrated that oral selenium and VitB₆ cosupplementation exerted synergism in lowering blood and liver lipid profiles and antiatherosclerotic effects in hyperlipidemic rats by reducing endogenous cholesterol and lipid synthesis, enhancing the transport of cholesterol to hepatocytes and promoting fatty acid beta oxidation.

Development of endometriosis involves alterations of many immunological factors, namely, secretion of chemokines and cytokines, recruitment, and expansion of immune cells and their interactions. These generate tolerant immune microenvironment for survival of ectopic endometrium. Such immunosuppressive mechanism in endometriosis facilitates endometrial cells escape from immunosurveillance, promote adhesion at ectopic site, induce pathological angiogenesis and stimulate proliferation. Immunotherapy targeting on the immunosuppressive cells, cytokines and molecular signaling pathways provide novel strategies for treatment of endometriosis. In this chapter, we aim to summarize the underlying mechanisms of immunosuppression and the crosstalk of different immune factors for potential immunotherapy in endometriosis.

Atorvastatin (ATO) is of the statin class and is used as an orally administered lipid-lowering drug. ATO is a reversible synthetic competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase thus leading to a reduction in cholesterol synthesis. It has recently been demonstrated that ATO has different pharmacological actions, which are unrelated to its lipid-lowering effects and has the ability to treat chronic airway diseases. This paper reviews the potential of ATO as an anti-inflammatory, antioxidant, and anti-proliferative agent after oral or inhaled administration. This paper discusses the advantages and disadvantages of using ATO under conditions associated with those found in the airways. This treatment could potentially be used to support the formulating of ATO as an inhaler for the treatment of chronic respiratory diseases.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spillover infection in December 2019 has caused an unprecedented pandemic. SARS-CoV-2, as other coronaviruses, binds its target cells through the angiotensin-converting enzyme 2 (ACE2) receptor. Accordingly, this makes ACE2 research essential for understanding the zoonotic nature of coronaviruses and identifying novel drugs. Here we present a systematic analysis of the ACE2 conservation and co-evolution protein network across 1,671 eukaryotes, revealing an unexpected conservation pattern in specific metazoans, plants, fungi, and protists. We identified the co-evolved protein network and pinpointed a list of drugs that target this network by using data integration from different sources. Our computational analysis found widely used drugs such as nonsteroidal anti-inflammatory drugs and vasodilators. These drugs are expected to perturb the ACE2 network affecting infectivity as well as the pathophysiology of the disease.

Inflammatory bowel disease is a chronic autoimmune disorder of the western world that is rapidly expanding in newly industrialized countries. Novel strategies are urgently needed to prevent and improve the treatment of this costly and disabling disease. Statins are the most commonly prescribed drugs worldwide. Besides their lipid-lowering effects, statins may exert complex immunomodulatory properties and multiple pleiotropic effects including the inhibition of T-cell activation, antigen-presenting function and leukocyte infiltration of target organs which might render statins as beneficial agents for inflammatory and autoimmune conditions. In this review, we summarize the experimental findings on the topic, and critically appraise the epidemiological evidence regarding the value of statins as a potential strategy for preventing and treating inflammatory bowel disease.

Several experimental studies have shown that statins reduce inflammation in animal models of colitis; however, clinical studies investigating their disease-modifying and preventive potential in IBD have demonstrated some limitations and conflicting results. The available epidemiological evidence is not yet sufficient to support the use of statin for preventing or treating inflammatory bowel disease. Additional high-quality research is warranted.