Pre-B cell colony enhancing factor (PBEF) is regarded as a proinflammatory cytokine. Named for its first discovered function as a pre-B cell colony enhancing factor, it has since been found to have many other functions relating to cell metabolism, inflammation, and immune modulation. It has also been found to have intracellular and extracellular forms, with the two overlapping in function. Most of the intracellular functions of PBEF are due to its role as a nicotinamide phosphoribosyltransferase (Nampt). It has been found in human endothelial cells, where it is able to induce angiogenesis through upregulation of VEGF and VEGFR and secretion of MCP-1. In human umbilical endothelial cells, PBEF increases levels of the protease MMP 2/9. PBEF has also been found in a variety of immune cells other than B cells and has been shown to inhibit apoptosis of macrophages. Extracellular PBEF has been shown to increase inflammatory cytokines, such as TNF-α, IL-1β, IL-16, and TGF-β1, and the chemokine receptor CCR3. PBEF also increases the production of IL-6, TNF-α, and IL-1β in CD14+ monocyctes, macrophages, and dendritic cells, enhances the effectiveness of T cells, and is vital to the development of both B and T lymphocytes. The purpose of this review is to summarize the recent advances in PBEF research.
pre-B cell enhancing factor; cytokine; chemikine; monocyte; B lymphocyte; T lymphocyte
The occurrence of intestinal polyps in people at high risk for developing colorectal cancer provides an opportunity to test the efficacy of chemoprevention agents. In this situation of treating otherwise healthy people, the potential for toxicity must be minimal. The small molecule flexible heteroarotinoid (Flex-Het), called SHetA2, has chemoprevention activity in organotypic cultures in vitro and lack of toxicity at doses capable of inhibiting xenograft tumor growth in vivo. The objective of this study was to evaluate SHetA2 chemoprevention activity and toxicity in the APCMin/+ murine model. Oral administration of SHetA2 at 30 and 60 mg/kg five days per week for 12 weeks significantly reduced development of intestinal polyps by 40 to 60% depending on the dose and sex of the treatment group. Immunohistochemical and Western blot analysis of polyps demonstrated reduced levels of cyclin D1 and proliferating cell nuclear antigen (PCNA) in both SHetA2 treatment groups. Western blot analysis also demonstrated SHetA2 induction of E-cadherin, Bax and caspase 3 cleavage along with reduction in Bcl-2, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), consistent with SHetA2 regulation of apoptosis, inflammation and angiogenesis. Neither dose caused weight loss nor gross toxicity in APCMin/+ or wild type littermates. Magnetic resonance imaging (MRI) of cardiac function showed no evidence of SHetA2 toxicity. SHetA2 did not alter left ventricular wall thickness. In summary, SHetA2 exerts chemoprevention activity without overt or cardiac toxicity in the APCMin/+ model. SHetA2 modulation of biomarkers in colon polyps identifies potential pharmacodynamic endpoints for SHetA2 clinical trials.
Chemoprevention; colon polyps; flexible heteroarotinoids; SHetA2; NSC721689
Chronic exposure to cold caused pulmonary arterial hypertension (CIPH) and increased phosphodiesterase-1C (PDE-1C) expression in pulmonary arteries (PAs) in rats. The purpose of this study is to investigate a hypothesis that inhibition of PDE-1 would decrease inflammatory infiltrates and superoxide production leading to attenuation of CIPH. Three groups of male rats were exposed to moderate cold (5±1°C) continuously while 3 groups were maintained at room temperature (23.5±1°C, warm) (6 rats/group). Following 8-week exposure to cold, 3 groups in each temperature condition received continuous i.v. infusion of 8-IBMX (PDE-1 inhibitor), apocynin (NADPH oxidase inhibitor) or vehicle, respectively, for one week. Cold exposure significantly increased right ventricular (RV) systolic pressure compared to warm groups (33.8±3.2 vs 18.6±0.3 mmHg), indicating that animals developed pulmonary arterial hypertension (CIPH). Notably, treatment with 8-IBMX significantly attenuated the cold-induced increase in RV pressure (23.5±1.8 mmHg). Cold exposure also caused RV hypertrophy while 8-IBMX reversed cold-induced RV hypertrophy. Cold exposure increased PDE-1C protein expression, macrophage infiltration, NADPH oxidase activity, and superoxide production in PAs and resulted in PA remodeling. 8-IBMX abolished cold-induced upregulation of PDE1C in PAs. Interestingly, inhibition of PDE1 eliminated cold-induced macrophage infiltration, NADPH oxidase activation, and superoxide production in PAs and reversed PA remodeling. Inhibition of NADPH oxidase by apocynin abolished cold-induced superoxide production and attenuated CIPH and PA remodeling.
Inhibition of PDE-1 attenuated CIPH and reversed cold-induced PA remodeling by suppressing macrophage infiltration and superoxide production, suggesting that upregulation of PDE-1C expression may be involved in the pathogenesis of CIPH.
pulmonary artery; blood pressure; remodeling; macrophage infiltration; NADPH oxidase; superoxide; smooth muscle cell proliferation; right ventricle
Pulmonary arterial hypertension (PAH) is characterized by a persistent elevation of pulmonary arterial pressure and pulmonary arterial remodeling with unknown etiology. Current therapeutics available for PAH are primarily directed at reducing the pulmonary blood pressure through their effects on the endothelium. It is well accepted that pulmonary arterial remodeling is primarily due to excessive pulmonary arterial smooth muscle cell (PASMC) proliferation that leads to narrowing or occlusion of the pulmonary vessels. Future effective therapeutics will be successful in reversing the vascular remodeling in the pulmonary arteries and arterioles. The purpose of this review is to provide updated information on molecular mechanisms involved in pulmonary arterial remodeling with a focus on growth factors, transcription factors, and epigenetic pathways in PASMC proliferation. In addition, this review will highlight novel therapeutic strategies for potentially reversing PASMC proliferation.
The normal IgG, a circulating antibody, is maintained at a constant level in humans. However, little is known if normal IgG has effects on the function of vascular endothelial cells. The purpose of this study was to investigate if IgG affects superoxide (O2-) generation and cell permeability in human aortic endothelial cells (HAECs) isolated from a hypertensive patient. The effect of normal human IgG on endothelial cell function was investigated in cultured HAECs isolated from a hypertensive patient who died of stroke. The results demonstrated, for the first time, that normal IgG attenuated the intracellular O2- level and decreased cell migration, cell permeability, and stress fiber formation in HAECs. IgG significantly decreased Rac1 activity and NADPH oxidase activity but upregulated MnSOD expression in HAECs, which may contribute to the IgG-induced decrease in O2- level. It is noted that AMPK was activated by IgG as evidenced by increased phosphorylation of AMPK (p-AMPK). Interestingly, inhibition of AMPK by an AMPK inhibitor (AI) abolished IgG-induced decreases in Rac1 and NADPH oxidase activities and IgG-induced increases in MnSOD expression, suggesting that AMPK is an important mediator of the IgG-induced regulation of these enzymes. Importantly, inhibition of AMPK activity also prevented the IgG-induced decrease in O2- levels, cell migration, cell permeability, and stress fiber formation. Therefore, normal human IgG may protect HAECs via activation of AMPK and subsequent decreases in intracellular O2-. These findings reveal a previously unidentified role of normal IgG in regulating AMPK and endothelial cell function.
IgG; superoxide; AMPK; NADPH oxidase; endothelial cell; permeability; migration
Clinical observations and epidemiological surveys indicated that the prevalence of hypertension and heart diseases is increased in cold regions or during winter. Cold exposure increased NADPH oxidase gp91phox protein expression in heart, kidneys, and aorta in rats. The aim of this study was to investigate if RNA interference (RNAi) silencing of gp91phox would attenuate cold-induced hypertension and cardiovascular and renal damage. The recombinant adeno-associated virus serotype 2 (AAV-2) vector carrying gp91phox-shRNA (gp91-shRNA) was constructed for inhibiting gp91phox protein expression in cold-exposed rats. Blood pressure (BP) was monitored using a telemetry system. BP was increased in the Control-shRNA and PBS groups within 1 week of exposure to moderate cold (5°C) and reached a plateau after 7 weeks. The cold-induced increase in BP was attenuated significantly by intravenous delivery of gp91-shRNA (1.25×1010 particles/rat, 0.5 mL). One single dose of gp91-shRNA controlled hypertension for up to 10 weeks. In addition, gp91-shRNA reversed cold-induced vascular dysfunction. gp91-shRNA abolished the cold-induced up-regulation of gp91phox protein expression in heart, kidneys, and aorta, confirming effective silencing of gp91phox. The cold-induced increases in NADPH oxidase activity and superoxide production were eliminated by silencing of gp91phox, suggesting that the cold-induced up-regulation of NADPH oxidase activity may be attributed to the increased gp91phox protein expression. RNAi silencing of gp91phox abolished cold-induced cardiac and renal hypertrophy and attenuated aortic, coronary, and renal remodeling. The up-regulation of gp91phox may play a critical role in cold-induced cardiovascular dysfunction and organ damage. AAV delivery of gp91-shRNA may be a new and effective therapeutic approach for cold-related cardiovascular disorders.
Wang and colleagues investigate silencing of gp91phox as a potential way to attenuate cold-induced hypertension and cardiovascular and renal damage. Recombinant adeno-associated virus serotype 2 (AAV2) carrying gp91phox–short hairpin RNA was constructed and delivered to cold-exposed rats. A single dose of vector controlled hypertension for up to 10 weeks and reversed cold-induced vascular dysfunction as well as renal hypertrophy.
Background and Hypothesis
Klotho is a recently discovered anti-aging gene. The purpose of this study was to investigate if klotho gene transfer attenuates superoxide production and oxidative stress in rat aorta smooth muscle (RASM) cells.
Methods and Results
RASM cells were transfected with AAV plasmids carrying mouse klotho full-length cDNA (mKL) or LacZ as a control. Klotho gene transfer increased klotho expression in RASM cells. Notably, klotho gene expression decreased Nox2 NADPH oxidase protein expression but did not affect Nox2 mRNA expression, suggesting that the inhibition may occur at the post-transcriptional level. Klotho gene transfer decreased intracellular superoxide production and oxidative stress in RASM cells. Klotho gene expression also significantly attenuated the angiotensin II (AngII)-induced superoxide production, oxidative damage, and apoptosis. Interestingly, klotho gene delivery dose-dependently increased the intracellular cAMP level and PKA activity in RASM cells. Rp-cAMP, a competitive inhibitor of cAMP, abolished the klotho-induced increase in PKA activity, indicating that klotho activated PKA via cAMP. Notably, inhibition of cAMP-dependent PKA activity by RP-cAMP abolished klotho-induced inhibition of Nox2 protein expression, suggesting an important role of the cAMP-dependent PKA in this process.
The present finding revealed a previously unidentified role of klotho in regulating Nox2 protein expression in RASM cells. Klotho not only downregulated Nox2 protein expression and intracellular superoxide production but also attenuated AngII-induced superoxide production, oxidative damage, and apoptosis. The klotho-induced suppression of Nox2 protein expression may be mediated by the cAMP PKA pathway.
klotho; Nox2; NADPH oxidase; superoxide; cAMP; PKA; smooth muscle cell
The purpose of this study was to test a hypothesis that T3 promotes glucose uptake via enhancing insulin-induced Akt phosphorylation and VAMP2 translocation in 3T3-L1 adipocytes. T3 significantly enhanced insulin-induced phosphorylation of Akt, cytoplasma to cell membrane translocations of vesicle-associated membrane protein 2 (VAMP2) and glucose transporter 4 (GLUT4), and glucose uptake in adipocytes. Akt inhibitor X abolished the promoting effects of T3, suggesting that Akt activation is essential for T3 to enhance these insulin-induced events in adipocytes. Knockdown of VAMP2 using siRNA abrogated the effects of T3 on insulin-induced GLUT4 translocation and glucose uptake, suggesting that VAMP2 is an important mediator of these processes. Conclusions - These data suggest that T3 may promote glucose uptake via enhancing insulin-induced phosphorylation of Akt and subsequent translocations of VAMP2 and GLUT4 in 3T3-L1 adipocytes. Akt phosphorylation is necessary for the promoting effects of T3 on insulin-stimulated VAMP2 translocation. Further, VAMP2 is essential for T3 to increase insulin-stimulated translocation of GLUT4 and subsequent uptake of glucose in adipocytes.
GLUT4; RNAi; T3; Akt; VAMP2
The purpose of this study was to determine changes in klotho, endothelin (ET) receptors, and superoxide production in kidneys of aged rats and whether these changes are exacerbated in aged rats with cognitive impairment. Twenty aged rats (male, 27 months) were divided into an Old Impaired group (n = 9) and an Old Intact group (n = 11) according to a cognitive function test. A group of 12-month-old rats (n = 10) was used as a Young Intact group. Serum creatinine was increased significantly in the Old Impaired group, suggesting impaired renal function. Aged rats showed glomerulosclerosis and tubulointerstitialfibrosis. These pathological changes were markedly aggravated in the old cognitively impaired than in the old cognitively intact animals. Notably, aged rats demonstrated a significant decrease in klotho protein expression in renal cortex and medulla. Protein expression of IL-6, Nox2, ETa receptors and superoxide production were increased whereas mitochondrial SOD (MnSOD) and ETb receptors expression were decreased in kidneys of the aged rats. Interestingly, these changes were more pronounced in the old impaired than in the old intact rats. In conclusion, the aging-related kidney damage was exacerbated in aged rats with cognitive impairment. Klotho, ETB, and MnSOD were downregulated but ETa, IL-6, Nox2, and superoxide production were upregulated in the aging-related kidney damage. These changes were more pronounced in rats with cognitive impairment.
Aging; Klotho; Glomerusclerosis; ET receptor; Superoxide; Interleukin-6
Background & Hypothesis
IL-10 is an anti-inflammatory cytokine. Nox1 is a mitogenic oxidase (p65-mox). The objective of this study was to test a hypothesis that IL10 deficiency would cause vascular remodeling via the upregulation of Nox1.
Methods & Results
Recombinant AAV carrying short hairpin small interference RNA for Nox1 (AAV.Nox1shRNA) was constructed for in vivo specific inhibition of Nox1. Three groups of IL10 gene knockout (IL10KO) mice and 3 groups of wild-type (WT) mice were used. Three groups of each strain received intravenous delivery of AAV.Nox1shRNA, AAV.ScrambledshRNA, and PBS, respectively. Animals were euthanized at 3 weeks after gene delivery. IL10KO increased Nox1 protein expression, NADPH oxidase activity, and superoxide production in aortas. IL10KO also resulted in a significant decrease in aortic medial thickness, a loss of smooth muscle cells, and an increase in vascular collagen deposition, indicating vascular remodeling. The IL10KO-induced increases in NADPH oxidase activity and superoxide production and vascular remodeling were abolished by silencing of p65-mox, suggesting that these effects may be mediated by the upregulation of Nox1. In addition, IL10KO increased endothelin-1 (ET-1) levels in plasma and aortas, and this effect was partially blocked by silencing of Nox1. RNAi silencing of Nox1 obliterated the IL10KO-induced increases in IL-6 expression in aortas, superoxide production and MMP-9 activity in aortic smooth muscle cells (SMC), and SMC migration.
IL10 is essential to the maintenance of normal vasculature as IL10 deficiency resulted in vascular damage and remodeling. The IL10KO-induced vascular structure damage may be mediated by the up-regulation of Nox1.
vascular remodeling; vascular smooth muscle cell; AAV; IL-6; MMP-9; ET-1; NADPH oxidase; superoxide
The purpose of this study was to determine the role of the pro-inflammatory cytokine IL-6 in cold-induced hypertension (CIH). Four groups of male Sprague Dawley rats were used (6 rats/group). After blood pressure (BP) was stabilized, 3 groups received intravenous delivery of AAV carrying IL-6shRNA, AAV carrying scrambled shRNA (ScrshRNA), and phosphate buffered solution (PBS), respectively, prior exposure to a cold environment (5°C). The last group received PBS and was kept at room temperature (25°C, warm) as a control. AAV delivery of IL-6shRNA significantly attenuated cold-induced elevation of systolic BP and kept it at the control level for up to 7 weeks (length of the study). Chronic exposure to cold up-regulated IL-6 expression in aorta, heart and kidneys and increased macrophage and T-cell infiltration in kidneys, suggesting that cold exposure increases inflammation. IL-6shRNA delivery abolished the cold-induced up-regulation of IL-6, indicating effective silence of IL-6. Interestingly, RNAi knockdown of IL-6 prevented cold-induced inflammation as evidenced by a complete inhibition of TNF-α expression and leukocyte infiltration by IL-6shRNA. RNAi knockdown of IL-6 significantly decreased the cold-induced increase in vascular superoxide production. It is noted that IL-6shRNA abolished the cold-induced increase in collagen deposition in the heart, suggesting that inflammation is involved in cold-induced cardiac remodeling. Cold exposure caused glomerular collapses which could be prevented by knockdown of IL-6, suggesting an important role of inflammation in cold-induced renal damage. Conclusions: Cold exposure increased IL-6 expression and inflammation which play a critical role in the pathogenesis of CIH and cardiac and renal damage.
cold exposure; inflammation; interleukin-6; short-hairpin siRNA; RNAi; adeno-associated virus
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by a persistent elevation of pulmonary artery pressure accompanied by right ventricular hypertrophy (RVH). The current treatment for pulmonary hypertension is limited and only provides symptomatic relief due to unknown etiology and pathogenesis of the disease. Both vasoconstriction and structural remodeling (enhanced proliferation of VSMC) of the pulmonary arteries contribute to the progressive course of PAH, irrespective of different underlying causes. The exact molecular mechanism of PAH, however, is not fully understood. The purpose of this review is to provide recent advances in the mechanistic investigation of PAH. Specifically, this review focuses on nitric oxide (NO), oxidative stress and inflammation and how these factors contribute to the development and progression of PAH. This review also discusses recent and potential therapeutic advancements for the treatment of PAH.
pulmonary arterial hypertension; pulmonary arterial remodeling; nitric oxide; cGMP; oxidative stress; NADPH oxidase; inflammation; cytokines; chemokines
Thyroid hormone (T3) can stimulate protein synthesis and cell growth. NOX1 is a mitogenic oxidase. The aim of this study was to test a novel hypothesis that T3 induces artery smooth muscle cell proliferation by up-regulating NOX1.
Methods and Results
Immunofluoresence confocal microscopy was used to visualize the sub-cellular localization of NOX1 and TRα1 in rat aorta smooth muscle (RASM) cells. Optical sectioning showed that TRα1 and NOX1 co-localized around the nucleus. T3 promoted RASM cell proliferation as determined by the fact that T3 significantly increased the number of cytokinesis cells, proliferating cellular nuclear antigen (PCNA), and smooth muscle α-actin (SM α-actin). T3 increased NOX1 expression at both the transcription (mRNA) and translation (protein) levels as evaluated by RT-PCR and western blot, respectively. T3 also significantly increased the intracellular ROS production based on the oxidation of 2’,7’-dichlorodihydrofluoresein (H2DCF) to a fluorescent 2’,7’-dichlorofluoresein (DCF). RNAi silence of TRα1 or NOX1 abolished T3-induced intracellular ROS generation and PCNA and SM α-actin expression, indicating that TRα1 and NOX1 mediated T3-induced RASM cell proliferation. Notably, RNAi silence of TRα1 blocked the T3-induced increase in NOX1 expression whereas silence of NOX1 did not affect TRα1 expression, disclosing a new pathway, i.e., T3-TRα1-NOX1-cell proliferation.
TRα1 and NOX1 co-localized around the nucleus. T3 induced RASM cell proliferation by up-regulating NOX1 in a TRα1-dependent manner.
thyroid hormone; TRα1; NOX1; ROS; smooth muscle cell; proliferation
The prevalence of hypertension is increased in winter and in cold regions of the world. Cold temperatures make hypertension worse and trigger cardiovascular complications (stroke, myocardial infarction, heart failure, etc.). Chronic or intermittent exposure to cold causes hypertension and cardiac hypertrophy in animals. The purpose of this review is to provide the recent advances in the mechanistic investigation of cold-induced hypertension (CIH). Cold temperatures increase the activities of the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS). The SNS initiates CIH via the RAS. Cold exposure suppresses the expression of eNOS and formation of NO, increases the production of endothelin-1 (ET-1), up-regulates ETA receptors, but down-regulates ETB receptors. The roles of these factors and their relations in CIH will be reviewed.
cold-induced hypertension; cold-induced cardiac hypertrophy; cold; blood pressure; sympathetic nervous system; renin-angiotensin system; endothelin; mineralocorticoid receptor; eNOS; c-myc
Type 2 diabetes mellitus (T2DM) affects a large population worldwide. T2DM is a complex heterogeneous group of metabolic disorders including hyperglycemia and impaired insulin action and/or insulin secretion. T2DM causes dysfunctions in multiple organs or tissues. Current theories of T2DM include a defect in insulin-mediated glucose uptake in muscle, a dysfunction of the pancreatic β-cells, a disruption of secretory function of adipocytes, and an impaired insulin action in liver. The etiology of human T2DM is multifactorial, with genetic background and physical inactivity as two critical components. The pathogenesis of T2DM is not fully understood. Animal models of T2DM have been proved to be useful to study the pathogenesis of, and to find a new therapy for, the disease. Although different animal models share similar characteristics, each mimics a specific aspect of genetic, endocrine, metabolic, and morphologic changes that occur in human T2DM. The purpose of this review is to provide the recent progress and current theories in T2DM and to summarize animal models for studying the pathogenesis of the disease.
Klotho is a recently discovered antiaging gene. The objective of this study was to test the hypothesis that klotho gene delivery attenuates the progression of spontaneous hypertension and renal damage in spontaneous hypertensive rats (SHRs). An adeno-associated virus (AAV) carrying mouse klotho full-length cDNA (AAV.mKL) was constructed for in vivo expression of klotho. Four groups of male SHRs and 1 group of sex- and age-matched Wistar-Kyoto rats (5 rats per group) were used. Blood pressure was measured twice in all of the animals before gene delivery. Four groups of SHRs received an IV injection of AAV.mKL, AAV.LacZ, AAV.GFP, and PBS, respectively. The Wistar-Kyoto group received PBS and served as a control. AAV.mKL stopped the further increase in blood pressure in SHRs, whereas blood pressures continued to increase in other SHR groups. One single dose of AAV.mKL prevented the progression of spontaneous hypertension for at least 12 weeks (length of the study). Klotho expression and production were suppressed in SHRs, which were reverted by AAV.mKL. AAV.mKL increased plasma interleukin 10 levels but decreased Nox2 expression, NADPH oxidase activity, and superoxide production in kidneys and aortas in SHRs. AAV.mKL abolished renal tubular atrophy and dilation, tubular deposition of proteinaceous material, glomerular collapse, and collagen deposition seen in SHRs, indicating that klotho gene delivery attenuated renal damage. Therefore, the suppressed klotho expression may play a role in the progression of spontaneous hypertension and renal damage in SHRs. AAV delivery of klotho may offer a new approach for the long-term control of hypertension and for renoprotection.
klotho; Nox2; blood pressure; adeno-associated virus; renoprotection
Klotho is a new anti-aging gene. Genetic mutation of klotho causes multiple premature aging-like phenotypes and strikingly shortens lifespan. Overexpression of the klotho gene in mice suppresses aging and extends lifespan which may involve the mechanism of suppression of insulin signaling and oxidant stress. Klotho functions as a cofactor/coreceptor regulating fibroblast growth factor (FGF) 23 signaling. Klotho acts as a glucuronidase and activates ion channel TRPV5. Klotho protects against endothelial dysfunction and regulates the production of nitric oxide. Klotho also influences intracellular signaling pathways including p53/p21, cAMP, protein kinase C (PKC) and Wnt signaling pathways. The discovery of klotho has a great impact on aging research. The purpose of this review is to provide the recent progress and future directions of klotho research. Specifically, this review will cover: klotho and aging, structure and expression of the klotho gene, localization of klotho expression, source of circulating klotho, current understanding of klotho functions, and signaling pathways of klotho.
klotho; aging; insulin signaling; fibroblast growth factor; glucuronidase; vitamin D
Molecular cardiology is a new and fast-growing area of cardiovascular medicine that aims to apply molecular biology techniques for the mechanistic investigation, diagnosis, prevention and treatment of cardiovascular disease. As an emerging discipline, it has changed conceptual thinking of cardiovascular development, disease etiology and pathophysiology. Although molecular cardiology is still at a very early stage, it has opened a promising avenue for understanding and controlling cardiovascular disease. With the rapid development and application of molecular biology techniques, scientists and clinicians are closer to curing heart diseases that were thought to be incurable 20 years ago. There clearly is a need for a more thorough understanding of the molecular mechanisms of cardiovascular diseases to promote the advancement of stem cell therapy and gene therapy for heart diseases. The present paper briefly reviews the state-of-the-art techniques in the following areas of molecular cardiology: gene analysis in the diseased heart; transgenic techniques in cardiac research; gene transfer and gene therapy for cardiovascular disease; and stem cell therapy for cardiovascular disease.
DNA; Genes; Heart diseases; Hypertrophy; Molecular biology; Myocardial infarction