Current Drug Targets - Cardiovascular & Hematological Disorders 

About: Current Drug Targets - Cardiovascular & Hematological Disorders is an academic journal published by Bentham Science Publishers. The journal publishes majorly in the area(s): Internal medicine & Chemistry. It has an ISSN identifier of 1871-529X. Over the lifetime, 125 publications have been published receiving 3956 citations. The journal is also known as: Cardiovasular and hematological disorders. Drug targets.

Microglia: neuroprotective and neurotrophic cells in the central nervous system.

Abstract: Microglia are currently accepted as sensor cells in the central nervous system that respond to injury and brain disease. The main function of microglia is believed to be brain defense, as they are known to scavenge invading microorganisms and dead cells, and also to act as immune or immunoeffector cells. However, microglia are also thought to contribute to the onset of or to exacerbate neuronal degeneration and/or inflammation in many brain diseases by producing deleterious factors including superoxide anions, nitric oxide and inflammatory cytokines. Nonetheless, microglia have also been shown to act neuroprotectively by eliminating excess excitotoxins in the extracellular space. Moreover, there is accumulating evidence that microglia produce neurotrophic and/or neuroprotective molecules; in particular, it has been suggested that they promote neuronal survival in cases of brain injury. In general, the question of whether microglia act as neurotoxic cells or as neuroprotective cells in vivo has gained much recent attention. In this paper, we provide a review of findings indicating that the microglia are basically neurotrophic/neuroprotective cells in the nervous system. In addition, the mechanism by which neurotrophic microglia become oriented to a neurotoxic state is discussed.

Remodeling of the myocardium and potential targets in the collagen degradation and synthesis pathways

Abstract: Remodeling of the myocardium is the major mechanism for disability and death in prevalent cardiovascular diseases such as hypertension, heart failure and myocardial infarction (MI) It is a complex process that involves changes in structure, shape and topography at the global level and changes in myocytes and non-myocytes at cellular and subcellular levels that impact negatively on function Although the myocytes subserve the heart's pump function, the predominant cell type in the heart is the fibroblast (not the myocyte) The fibroblast's major role is deposition of the extracellular matrix (ECM) of which collagen is the principal component The cardiac extracellular collagen matrix (ECCM) maintains structural and functional integrity, and contributes to coordinated mechanical action with every systole during life Excessive collagen deposition or pathological fibrosis is an important contributor to left ventricular (LV) dysfunction and poor outcome in hypertension, MI and heart failure It is also an important problem in the aging heart Antifibrotic agents that target steps in the collagen synthesis and degradation pathways therefore represent promising strategies for these diseases Because reparative fibrosis is an essential component of healing of the infarct zone (IZ) after MI, the design of approaches that separately target the IZ and non-infarct zone (NIZ) is challenging It may be possible in future to target the collagen pathways in the heart or regions of the heart, and not other areas or organs, by delivering drugs or genes locally to specific regions

Biological properties of baicalein in cardiovascular system

Abstract: The dried roots of Scutellaria baicalensis (S. baicalensis) Georgi (common name: Huangqin in China) have been widely employed for many centuries in traditional Chinese herbal medicine as popular antibacterial and antiviral agents. They are effective against staphylococci, cholera, dysentery, pneumococci and influenza virus. Baicalein, one of the major flavonoids contained in the dried roots, possesses a multitude of pharmacological activities. The glycoside of baicalein, baicalin is a potent anti-inflammatory and anti-tumor agent. This review describes the biological properties of baicalein (Table 1), which are associated with the prevention and treatment of cardiovascular diseases. Baicalein is a potent free radical scavenger and xanthine oxidase inhibitor, thus improving endothelial function and conferring cardiovascular protective actions against oxidative stress-induced cell injury. Baicalein lowers blood pressure in renin-dependent hypertension and the in vivo hypotensive effect may be partly attributed to its inhibition of lipoxygenase, resulting in reduced biosynthesis and release of arachidonic acid-derived vasoconstrictor products. On the other hand, baicalein enhances vasoconstricting sensitivity to receptor-dependent agonists such as noradrenaline, phenylephrine, serotonin, U46619 and vasopressin in isolated rat arteries. The in vitro effect is likely caused by inhibition of an endothelial nitric oxide-dependent mechanism. The anti-thrombotic, anti-proliferative and anti-mitogenic effects of the roots of S. baicalensis and baicalein are also reported. Baicalein inhibits thrombin-induced production of plasminogen activator inhibitor-1, and interleukin-1beta- and tumor necrosis factor-alpha-induced adhesion molecule expression in cultured human umbilical vein endothelial cells. The pharmacological findings have highlighted the therapeutic potentials of using plant-derived baicalein and its analogs for the treatment of arteriosclerosis and hypertension.

Hyaluronan and hyaluronan synthases: potential therapeutic targets in cancer.

Abstract: Current models of oncogenesis describe cancer as a progression of genetic mutations in a tumor cell mass. However, tumors are more than a clonal expansion of malignant cells. Tumors are heterogeneous, with a complex 3D structure, analogous to organs comprised of different tissues. In a tumor mass, the component cell types interact with each other and with their microenvironment by exchanging information through cell-cell interactions and/or through interactions with the extracellular matrix (ECM). These synergetic interactions facilitate tumor progression. Furthermore, tumor invasion and metastatic development are accomplished through the breakdown of ECM. Disruption of ECM promotes abnormal inter- and/or intra- cellular signaling, leading to dysregulation of cell proliferation, growth and cytoskeleton reorganization. The disruption of the ECM in turn promotes the overproduction of growth factors, which induce elevated epithelial cell proliferation and other abnormalities including carcinogenesis. In this review we will demonstrate that hyaluronan (HA), a core component of ECM, contributes to certain types of cancer development. Additional to extracellular HA, intracellular and nuclear forms of HA have been detected. Intracellular HA is involved in cell signaling, whereas nuclear HA could promote chromatin condensation and thus facilitate mitosis. HA molecules are synthesized by hyaluronan synthases (HASs)-HAS1, HAS2 and HAS3 enzymes. Dysregulation of HAS genes results in abnormal production of HA and promotion of abnormal biological processes such as transformation and metastasis. The function of HASs appears to be cell and tissue specific. HAS1 maintains a low, basal level of HA. HAS2 is involved in embryonic and cardiac cushion morphogenesis and subsequent development through cell migration and invasion. HAS2 stimulates cell proliferation and angiogenesis. HAS3 appears to favor the malignant phenotype in many types of malignancies. However, the exact function of HAS isoenzymes and their role in cell signaling remains to be elucidated. A better understanding of HA and HASs may facilitate the design of novel therapeutic strategies to counter presumptive cancer-promoting effects of microenvironmental components.

Critical limb ischemia: definition and natural history.

Abstract: The term critical limb ischemia refers to a condition characterized by chronic ischemic at-rest pain, ulcers, or gangrene in one or both legs attributable to objectively proven arterial occlusive disease. Critical limb ischemia implies chronicity and is to be distinguished from acute limb ischemia. Its incidence is approximately 500 to 1000 per million year, with the highest rates among older subjects, smokers and diabetics. The rate of primary amputation ranges from 10% to 40%, and was performed only when no graftable distal vessels were present, or in neurologically impaired or hopelessly nonambulatory patients. Contrarily, in some highly specialized and aggressive centres about 90% of patients with CLI had an attempted revascularization. Furthermore, patients with critical limb ischemia have an elevated risk of future myocardial infarction, stroke and vascular death, 3-fold higher than patients with intermittent claudication. Therefore, due to its negative impact on the quality of life and the poor prognosis both in terms of limb salvage and survival, critical limb ischemia is a critical public health issue.