Autophagy and myocardial ischemia/reperfusion injury

Autophagy is a lysosome-dependent degradative pathway which is characterized by cytoplasmic vacuolization. However, it is not just a simple degradative pathway. Research shows that autophagy is related to many diseases, such as neurodegenerative disease, malignant tumor, ageing, pathogenic microorganism infection, myocardial ischemia/reperfusion injury and so on. Autophagy exactly exists in myocardial ischemia/reperfusion injury, and it becomes a new research hotspot. This review will focus on the occurrence and development of autophagy and its role, signal transduction and research status in myocardial ischemia/reperfusion injury.     

Clock genes and cardiovascular diseases

The biorhythms of every species are precisely regulated to adapt the environmental changes. The function of biorhythms is controlled by the clock genes in either a single cell or the whole body. The function of clock genes depends on the feedback circles that are composed by the interactions among the clock components. Many studies indicate that circadian clock is closely related to diseases. Several cardiovascular diseases such as myocardial ischemia and myocardial infarction show overt circadian rhythms, indicating that clock genes may play an important role in such kinds of diseases.     

Cellular and molecular mechanisms of electrical remodeling in cardiac ventricle after myocardial infarction

Arrhythmia is common in cardiovascular diseases, especially after myocardial infarction. This article reviews the electrophysiologic changes following myocardial infarction at different phases. Modulations of ion channel function that might contribute to electrical remodeling, such as cellular (autocrine/paracrine) factors and regulators of ion channel gene, are discussed. Unresolved problems in ventricular electrical remodeling after myocardial infarction are also considered.     

Investigation progress of CaSR in cardiovascular system

Calcium sensing receptors (CaSR) is a member of super-family of G-protein coupling receptors. This review first introduced the concept, construction features, distribution, functions, decision methods, moderators, genetic locus of CaSR and its relationship with some diseases concisely. Then this article described the investigation progress of CaSR in cardiovascular system intensively, including the expression pattern, role and signal pathways of CaSR in rat myocardium in normal, ischemia-reperfusion injury, apoptosis and cardiac hypertrophy; the role and mechanism of CaSR in calcium homostasis regulation of rat myocardium, endoplasmic reticulum (ER) stress and cardiac ischemic preconditioning and postconditioning. The metabolism rule, physiological significance and pathological action of polyamine in cardiac cells; the increase of CaSR expression in cardiac tissue of artherosclerosic rat and its effect on sensitivity to acute myocardial infarction are also discussed. In the end, the research perspective of CaSR in cardiovascular system was anticipated.     

Roles of mitochondrial dysfunction in cardiovascular diseases

Mitochondria are important organelles of energy generation in eukaryocytes and play a pivotal role in cell calcium homeostasis, signal transduction and apoptotic regulation. The possible causes leading to mitochondrial dysfunction include oxidative stress, Ca2+ disorder, reduction of mitochondrial biosynthesis and mitochondrial DNA mutations, all of which are also closely related to the development of cardiovascular diseases. Understanding the mitochondrial dysfunction and its important role in cardiovascular diseases are very significant for elucidating the mechanisms of cardiovascular diseases.     

Discovery of 20-HETE receptor and its effects on hypertension

20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoactive eicosanoid discovered in recent years, which has multiple vascular effects including stimulation of smooth muscle contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Clinical and experimental research suggests that 20-HETE is an important mediator of cardiovascular function, and plays a critical role in the pathogenesis of hypertension, stroke, myocardial infarction and vascular diseases. Recently, G-protein-coupled receptor 75 (GPR75) was identified as a 20-HETE receptor and mediated the development of 20-HETE-dependent hypertension. The discovery of 20-HETE-GPR75 pairing provides the molecular basis for the signaling and pathophysiological functions mediated by 20-HETE in hypertension and cardiovascular diseases. In this brief review, we discuss the recent findings related to the effects of 20-HETE in the pathogenesis of hypertension and the discovery and effects of GPR75.     

Function and significance of integrin-linked kinase in heart

Integrin-linked kinase (ILK) is a widely expressed protein kinase that relate to cellular growth and differentiation. It is most abundant in the heart. Recently, many researches revealed that ILK is highly relevant to cardiac response to biomechanical stresses. Also, ILK plays important roles in regulation of the occurrence and development of cardiac hypertrophy, dilated cardiomyopathy, viral myocarditis and myocardial senescence via correlation to several classical signal transduction pathway. Meanwhile, ILK functions in protection after myocardial infarction. This article will try to summarize the effects and relevant mechanism of ILK in above-mentioned aspects, overall reveals the roles of ILK in heart and its potential clinical significance.     

Effect of bFGF on promoting angiogenesis in infarct area and improving myocardial fibrosis in mouse myocardial infarction model

AIM: To investigate the protective effect of basic fibroblast growth factor (bFGF) on the heart of mice with myocardial infarction and its mechanism. METHODS: The model of myocardial infarction was established by the ligation of left anterior descending artery of C57/B6 mice (8~12 weeks old) after lateral thoracotomy. The mice were divided into sham operation group, myocardial infarction group and bFGF administration group. bFGF at 0.5 μg was intraperitoneally injected on alternate days after myocardial infarction for 7 d. Cardiac Doppler ultrasonography was used to detect cardiac function after myocardial infarction for 28 d, and left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction and left ventricular shortening fraction (LVFS) were used to evaluate cardiac function. After myocardial infarction for 28 d, the mice were sacrificed and the hearts were collected for preparing pathological sections. The degrees of myocardial fibrosis and angiogenesis in the myocardial infarction area were observed. Western blot was used to detect the indicators of angiogenesis. RESULTS: The results of Masson staining showed that bFGF administration significantly reduced myocardial fibrosis at 28 d after myocardial infarction. Cardiac ultrasound data showed that cardiac functions in myocardial infarction group were poorer than those in sham group, and bFGF administration significantly improved cardiac functions. Immunofluorescence staining showed that neovascularization in myocardial infarction area of bFGF administration group was more than that in myocardial infarction group. The results of Western blot showed that bFGF activated AKT/HIF-1α/VEGF signaling pathway. CONCLUSION: Intraperitoneal injection of bFGF reduces myocardial fibrosis and improves cardiac function in myocardial infarction mice. bFGF may promote angiogenesis by activating AKT/HIF-1α/VEGF signaling pathway.     

Lysophosphatidic acid and phenotypic modulation in vascular smooth muscle cells

Lysophosphatidic acid (LPA) is a sort of phospholipid messenger possessing diverse physiological role, which is mediated by its G protein-coupled receptors, and plays a significant role in vascular diseases. Phenotypic modulation of vascular smooth muscle cells (VSMCs) is the key initiation step of VSMCs proliferation and migration in hypertension, atherosclerosis and postangioplasty restenosis, and is the common morbility foundation of these vascular diseases. In this article we briefly review the LPA biological characteristics, its relationship with VSMCs phenotypic modulation and relative signal transduction pathway.     

Progress of STIM1, a dynamic calcium signal transducer, #br# in cardiovascular diseases

Stromal interaction molecule 1 (STIM1) is a transmembrane protein of the endoplasmic reticulum (ER), a Ca²⁺ transducer in ER that activates the store-operated calcium channel. Through Orai1 protein, STIM1 adjusts the intracellular and extracellular calcium concentration. This way is called a store-operated Ca²⁺ entry. STIM1 plays a key role in phenotypic transformation of vascular smooth muscle cells, proliferation of endothelial cells, myocardial hypertrophy and myocardial fibrosis to regulate lots of cardiovascular diseases, such as atherosclerosis, congestive heart failure and systemic hypertension. STIM1 is closely related to cardiovascular diseases through calcium signal. The research progress of STIM1 in cardiovascular diseases is mainly discussed in this article.     

Regulating autonomic nerve system: a new field of anti-inflammatory therapy for cardiovascular diseases

The role of chronic inflammation and autonomic neuropathy in the crucial underlying process contributing to the initiation and the progression of various cardiovascular diseases is well established. It is well known that the immune system is innervated by the autonomic nervous system, and the inflammatory reaction and immune reaction are re-gulated by the autonomic nerve system. Vagus nerve depresses inflammatory reaction via cholinergic anti-inflammatory pathway(CAP), while sympathetic nervous system has bidirectional regulation of pro-inflammation and anti-inflammation, which are affected by several factors such as the concentration of neurotransmitters or types of receptors. In this paper, we reviewed different effects of CAP and sympathetic nervous system on cardiovascular inflammatory reaction. Activation of CAP and regaining normal sympathetic function will improve the chronic inflammation in the process of cardiovascular diseases. Low-toxic and selective α7nAchR agonist is expected to be applied in cardiovascular diseases to alleviate chronic inflammation.     

Effects of naringenin on PI3K/AKT signaling pathway and endoplasmic reticulum stress and its related apoptotic pathways in rats with myocardial ischemia/reperfusion injury

AIM To observe the effect of naringenin on cardiac injury in ischemia/reperfusion （I/R） rats, and to explore whether the role of naringenin is involved in PI3K/AKT signaling pathway and endoplasmic reticulum stress and its related apoptotic pathways. METHODS SD rats （n=48） were randomly divided into sham operation （sham） group, model （I/R） group, naringenin treatment （NAR） group and naringenin+LY294002 （NL） group. Myocardial I/R injury model was prepared by ligation of left anterior descending coronary artery of rats for 30 min followed by reperfusion for 120 min. After reperfusion, the serum levels of cardiac troponin I （cTnI） was measured by ELISA. HE staining, TTC staining and TUNEL staining were used to detect the myocardial histopathological changes, myocardial infarction area and myocardial cell apoptotic rate. The mRNA levels of endoplasmic reticulum stress-related indicators glucose-regulated protein 78 （GRP78）, C/EBP homologous protein （CHOP） and caspase-12 were detected by RT-qPCR. The protein levels of cleaved caspase-3, GRP78, CHOP, caspase-12, p-PI3K and p-AKT were determined by Western blot. RESULTS Compared with I/R group, the serum content of cTnI, myocardial pathological damage, myocardial infarction area and myocardial cell apoptotic rate were significantly reduced （P<0.05）, the protein levels of cleaved caspase-3, GRP78, CHOP and caspase-12 were decreased （P<0.05）, and the protein levels of p-PI3K and p-AKT were increased in NAR group （P<0.05）. LY294002 attenuated the protective effect of naringenin to some extent. CONCLUSION Naringenin reduces myocardial I/R injury in rats possibly by activating PI3K/AKT signaling pathway and subsequently regulating endoplasmic reticulum stress and its related apoptotic pathways.     

Research progress in prorenin and prorenin receptor

The renin-angiotension system (RAS) plays an important role in cardiovascular and renal physiology and diseases. Recent discoveries of prorenin and prorenin receptor add new contents to RAS. Renin and prorenin binding to the prorenin receptor not only target and facilitate angiotensin generation but also lead to activation of prorenin receptor signal transduction pathways, which is distinct from classical RAS signaling. In this paper, the construction, function and signal trasduction of prorenin, prorenin receptor and handle region peptide are reviewed.     

Recent progresses on the study of endotoxin-induced p38 MAPK signal transduction

The diseases caused by endotoxin have seriously affected human health. Previous studies have shown that p38 MAPK pathway is involved in the intracellular signal transduction induced by lipopolysaccharide (LPS), which plays an important role in the activation of inflammation-related cells to release inflammation mediator. Recently there have been some progresses in the isoforms distribution, substrate, molecular mechanism of regulating the release of inflammatory mediators, cellular specific activation and levels of p38 MAPK.     

Integrins and cardiovascular diseases

The adhesion of cells to each other and to the proteins of the extracellular matrix provides a stable environment for cell growth, differentiation and migration. This is a prerequisite for the normal function of the cardiovascular system. Thus the abnormal adhesion function may play a key role in the pathogenesis and development of cardiovascular diseases. To date, there are six main groups of adhesion molecule, and integrins family are the largest and most broadly distributed of the families of cellular adhesion receptors. They have an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction in incidence andmortality due to these disorders. This review focuses upon the structure, mechanism and their roles in cardiovascular diseases which maybe facilitate the development of novel therapies.     

PTEN and signal transduction and tumor

PTEN is a candidate tumor suppressor which has sequence homology withdual-specifici-ty phosphatase. PTEN is a multifunctional protein endowed with a phosphatase activity capable of dephosphory-lating both tyrosine phosphate, serine/threonine phosphate residues on proteins and phospholipids of the phosphati dylinositol pathway. PTEN appears to be mutated at considerable frequency in several types of humantumors, including those frombrain, breast, endometrium, and prostate. PTEN play an important role in pathogenesis of tumor, tumor cell invasion and metastasis. In this review, we will discuss the chemical structure of PTEN, its phosphatase activity, the ability of affecting signal transduction, and its mutational status in cancer.     

Progress in role of lncRNA in cardiovascular diseases

Cardiovascular diseases are closely related to proliferation, injury and apoptosis of the cells in the cardiovascular system. For instance, endothelial cells play an important role in the pathogenic process of hypertension and atherosclerosis, and smooth muscle cells and monocytes/macrophages involve in the formation of atherosclerotic plaque. Recently, it has been confirmed that long noncoding RNA (lncRNA) regulates proliferation, apoptosis, injury, autophagy and differentiation of the cells by a series of regulatory mechanisms, thus participating in the development and progression of cardiovascular diseases. This article is to review the recent research progress on the function of lncRNAs and their regulatory roles in the cardiovascular diseases at cellular and molecular levels.     

Astragaloside IV promotes angiogenesis in rats with myocardial infarction via PKD1-HDAC5-VEGF pathway

AIM: To investigate the angiogenic effect and mechanisms of astragaloside IV (AS-IV) in rats with myocardial infarction via protein kinase D1 (PKD1)-histone deacetylase 5 (HDAC5)-vascular endothelial growth factor (VEGF) signaling pathway. METHODS: The classic model of myocardial infarction by ligation of the left anterior descending coronary artery was replicated, and the rats were randomly divided into model group, AS-IV group, and AS-IV+CID755673 (PKD1 inhibitor) group. The sham operation control group and DMSO control group were also set up. All the rats were given intravenous injection via caudal vein. The rats were sacrificed 4 weeks later, and segmental heart samples were used for HE staining and Masson staining. The expression of PKD1, HDAC5 and VEGF was analyzed by immunohistochemistry, RT-PCR and and Western blot. RESULTS: Compared with sham operation group and DMSO group, the myocardium in model group showed disordered arrangement, accompanied with necrotic myocardial cells and obvious fibrosis tissue. After treatment with AS-IV, the morphological changes of myocardium were obviously improved, and the number of new blood vessels increased significantly. However, after treatment with AS-IV+CID755673, the myocardial tissues of the rats became disordered again, with increased necrotic cells and some closed vessels. The mRNA and protein expression of PKD1, HDAC5 and VEGF in myocardial tissue in model group was significantly lower than that in sham operation and DMSO groups (P<0.05). The expression in AS-IV group was significantly higher than that in model group (P<0.01), while that in AS-IV+ CID755673 group was significantly lower than that in AS-IV group (P<0.05). CONCLUSION: AS-IV promotes the angiogenesis of myocardial tissues in the rats after myocardial infarction partly by regulating the PKD1-HDAC5-VEGF signaling pathway.