Therapeutic Potential of Systemic Gene Transfer Strategy for Hypertension and Cardiovascular Disease

2007 ◽  
pp. 429-445 ◽  
Author(s):  
Shant Der Sarkissian ◽  
Mohan K. Raizada
Keyword(s):  
Cardiovascular Disease ◽  
Gene Transfer ◽  
Therapeutic Potential

scholarly journals Therapeutic Potential of Gene Transfer to Testis; Myth or Reality?

10.5772/20488 ◽  
2011 ◽  
Author(s):  
Yoshiyuki Kojima ◽  
Kentaro Mizuno ◽  
Yukihiro Umemoto ◽  
Shoichi Sasaki ◽  
Yutaro Hayashi ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Therapeutic Potential

Hydrogen sulfide-mediated cardioprotection: mechanisms and therapeutic potential

2010 ◽  
Vol 120 (6) ◽  
pp. 219-229 ◽  
Author(s):  
Madhav Lavu ◽  
Shashi Bhushan ◽  
David J. Lefer
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Hydrogen Sulfide ◽  
Therapeutic Potential ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Signalling Molecule ◽  
Anti Inflammatory ◽  
Antioxidant Effects

H2S (hydrogen sulfide), viewed with dread for more than 300 years, is rapidly becoming a ubiquitously present and physiologically relevant signalling molecule. Knowledge of the production and metabolism of H2S has spurred interest in delineating its functions both in physiology and pathophysiology of disease. Although its role in blood pressure regulation and interaction with NO is controversial, H2S, through its anti-apoptotic, anti-inflammatory and antioxidant effects, has demonstrated significant cardioprotection. As a result, a number of sulfide-donor drugs, including garlic-derived polysulfides, are currently being designed and investigated for the treatment of cardiovascular conditions, specifically myocardial ischaemic disease. However, huge gaps remain in our knowledge about this gasotransmitter. Only by additional studies will we understand more about the role of this intriguing molecule in the treatment of cardiovascular disease.

Abstract 2103: Prevention of Pulmonary Hypertension by ACE2 Gene Transfer to Lungs

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Yoriko Yamazato ◽  
KwonHo Hong ◽  
Dae Song Jang ◽  
Anderson J Ferreira ◽  
Masanobu Yamazato ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Gene Transfer ◽  
Wall Thickness ◽  
Lentiviral Vector ◽  
Therapeutic Potential ◽  
Systolic Pressure ◽  
Vector Particle ◽  
Mrna Levels ◽  
Alveolar Cells ◽  
Ace2 Gene

Pulmonary hypertension (PH) is characterized by increase in pulmonary vascular resistance, and narrowing and loss of pulmonary microvasculare. There is an indispensable need to develop innovative approaches for its control since PH becomes refractory to current therapies in later stages. Recent discovery of angiotensin converting enzyme 2 (ACE2), its involvement in cardiac remodeling, coupled with the limited success of ACE inhibitors in PH has led us to hypothesize that shifting the balance of renin-angiotensin system (RAS) to vasoprotective ACE2-Ang1–7- mas receptor axis would result the beneficial outcome in PH. We tested this hypothesis with the use of ACE2 overexpression in lungs by lentiviral vector-mediated gene transfer. Lentiviral vector particle(3x10^8 TU) containing murine ACE2 (letni-ACE2) were injected into 6 weeks old C57BL/6 mice prior to induction of PH by administration of weekly 600 mg/kg of monocrotaline (MCT) for 8 weeks for prevention studies. In addition, lenti-ACE2 was delivered following 6 weeks MCT treatment in reversal studies. Right ventricle systolic pressure (RVSP), Real-time RT-PCR, immunohisitochemistory of ACE2 and Ang (1–7) and histology of lungs in control and lent-ACE2 treated mice were carried out to evaluated the outcome on PH. Delivery of lenti-ACE2 resulted in a long-term increase in ACE2 expression in the lungs. A 60% and 100 % increases in protein and mRNA levels for ACE2 were observed. ACE2 and Ang (1–7) immunoreactivity were observed in epithelial and alveolar cells and alveolar macrophages. MCT treatment increased in RVSP (MCT 44.5+/−5.7 mmHg, control 24+/−1.0mmHg), RV hypertrophy (RV/LV+Sp ratio; 0.31+/−0.01), and wall thickness of pulmonary vessels. ACE2 gene transfer prevented increases in RVSP (26.1+/− 1.1mmHg), and RV hypertrophy (0.26+/−0.1), and reduced vessel wall thickness. In addition, ACE2 overexpression resulted in a significant reversal of RVSP (23.5+/−0.6mmHg). Futhermore, ACE2 overexpression in mice exhibited better general appearance and gained weight compared to MCT-treated mice. ACE2 gene transfer to lungs prevents and reverses vascular remodeling and PH in MCT model of PH. These observations suggest that targeting of pulmonary ACE2 holds novel therapeutic potential for PH.

scholarly journals Navigating the Crossroads of Cell Therapy and Natural Heart Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Stefan Elde ◽  
Hanjay Wang ◽  
Y. Joseph Woo
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Cell Therapy ◽  
Cause Of Death ◽  
Natural Regeneration ◽  
Therapeutic Potential ◽  
Myocardial Regeneration ◽  
Heart Regeneration ◽  
Recent Developments

Cardiovascular disease remains the leading cause of death worldwide despite significant advances in our understanding of the disease and its treatment. Consequently, the therapeutic potential of cell therapy and induction of natural myocardial regeneration have stimulated a recent surge of research and clinical trials aimed at addressing this challenge. Recent developments in the field have shed new light on the intricate relationship between inflammation and natural regeneration, an intersection that warrants further investigation.

Adrenomedullin: angiogenesis and gene therapy

2005 ◽  
Vol 288 (6) ◽  
pp. R1432-R1437 ◽  
Author(s):  
Noritoshi Nagaya ◽  
Hidezo Mori ◽  
Shinsuke Murakami ◽  
Kenji Kangawa ◽  
Soichiro Kitamura
Keyword(s):  
Gene Transfer ◽  
Cell Biology ◽  
Therapeutic Potential ◽  
Lattice Structure ◽  
Rabbit Model ◽  
Mitogen Activated Protein Kinase ◽  
Tissue Ischemia ◽  
Hypoxic Conditions

Adrenomedullin (AM) is a potent, long-lasting vasodilator peptide that was originally isolated from human pheochromocytoma. AM signaling is of particular significance in endothelial cell biology since the peptide protects cells from apoptosis, promotes angiogenesis, and affects vascular tone and permeability. The angiogenic effect of AM is mediated by activation of Akt, mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2, and focal adhesion kinase in endothelial cells. Both AM and its receptor, calcitonin receptor-like receptor, are upregulated through a hypoxia-inducible factor-1-dependent pathway under hypoxic conditions. Thus AM signaling plays an important role in the regulation of angiogenesis in hypoxic conditions. Recently, we have developed a nonviral vector, gelatin. Positively charged gelatin holds negatively charged plasmid DNA in its lattice structure. DNA-gelatin complexes can delay gene degradation, leading to efficient gene transfer. Administration of AM DNA-gelatin complexes induces potent angiogenic effects in a rabbit model of hindlimb ischemia. Thus gelatin-mediated AM gene transfer may be a new therapeutic strategy for the treatment of tissue ischemia. Endothelial progenitor cells (EPCs) play an important role in endothelial regeneration. Interestingly, EPCs phagocytose ionically linked DNA-gelatin complexes in coculture, which allows nonviral gene transfer into EPCs. AM gene transfer into EPCs inhibits cell apoptosis and induces proliferation and migration, suggesting that AM gene transfer strengthens the therapeutic potential of EPCs. Intravenous administration of AM gene-modified EPCs regenerate pulmonary endothelium, resulting in improvement of pulmonary hypertension. These results suggest that in vivo and in vitro transfer of AM gene using gelatin may be applicable for intractable cardiovascular disease.

Scalable and reversible axonal neuromodulation of the sympathetic chain for cardiac control

2021 ◽  
Author(s):  
Joseph Hadaya ◽  
Una Buckley ◽  
Nil Z. Gurel ◽  
Christopher A. Chan ◽  
Mohammed A Swid ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Therapeutic Potential ◽  
Distal Portion ◽  
Left Ventricular ◽  
Sympathetic Chain ◽  
Strong Correlations ◽  
Norepinephrine Release ◽  
Ventricular Activation ◽  
Current Block ◽  
The Right

Maladaptation of the sympathetic nervous system contributes to the progression of cardiovascular disease and risk for sudden cardiac death, the leading cause of mortality worldwide. Axonal modulation therapy (AMT) directed at the paravertebral chain blocks sympathetic efferent outflow to the heart, and may be a promising strategy to mitigate excess disease-associated sympathoexcitation. The present work evaluates AMT, directed at the sympathetic chain, in blocking sympathoexcitation using a porcine model. In anesthetized porcine (n=14), we applied AMT to the right T1-T2 paravertebral chain and performed electrical stimulation of the distal portion of the right sympathetic chain (RSS). RSS-evoked changes in heart rate, contractility, ventricular activation recovery interval (ARI), and norepinephrine release were examined with and without kilohertz frequency alternating current block (KHFAC). To evaluate efficacy of AMT in the setting of sympathectomy, evaluations were performed in the intact state and repeated after left and bilateral sympathectomy. We found strong correlations between AMT intensity and block of sympathetic stimulation-evoked changes in cardiac electrical and mechanical indices (r=0.83-0.96, effect size d=1.9-5.7), as well as evidence of sustainability and memory. AMT significantly reduced RSS-evoked left ventricular interstitial norepinephrine release, as well as coronary sinus norepinephrine levels. Moreover, AMT remained efficacious following removal of the left sympathetic chain, with similar mitigation of evoked cardiac changes and reduction of catecholamine release. With growth of neuromodulation, an on-demand or reactionary system for reversible AMT may have therapeutic potential for cardiovascular disease-associated sympathoexcitation.

scholarly journals The Role of Simvastatin in the Therapeutic Approach of Rheumatoid Arthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Lucia Cojocaru ◽  
Andrei Constantin Rusali ◽  
Cristina Şuţa ◽  
Anca Mihaela Rădulescu ◽  
Maria Şuţa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Active Rheumatoid Arthritis ◽  
Therapeutic Potential ◽  
Efficacy And Safety ◽  
Good Safety Profile ◽  
Study Support ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The pleiotropic effects of statins, especially the anti-inflammatory and immunomodulatory ones, indicate that their therapeutic potential might extend beyond cholesterol lowering and cardiovascular disease to other inflammatory disorders such as rheumatoid arthritis. Therefore, we undertook a prospective cohort study to evaluate the efficacy and safety of simvastatin used for inflammation control in patients with rheumatoid arthritis. One hundred patients with active rheumatoid arthritis divided into two equal groups (the study one who received 20 mg/day of simvastatin in addition to prior DMARDs and the control one) were followed up over six months during three study visits. The results of the study support the fact that simvastatin at a dose of 20 mg/day has a low anti-inflammatory effect in patients with rheumatoid arthritis with a good safety profile.

scholarly journals Novel Insights From Human Studies on the Role of High-Density Lipoprotein in Mortality and Noncardiovascular Disease

2020 ◽  
Author(s):  
Christian M. Madsen ◽  
Anette Varbo ◽  
Børge G. Nordestgaard
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Therapeutic Potential ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Cancer Type ◽  
Health And Disease ◽  
And Function

The vast majority of research about HDL (high-density lipoprotein) has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within cardiovascular disease prevention; however, failures with therapies aimed at increasing HDL cholesterol has left questions as to what the role and function of HDL in human health and disease is. Recent observational studies have further shown that extreme high HDL cholesterol is associated with high mortality leading to speculations that HDL could in some instances be harmful. In addition, evidence from observational, and to a lesser extent genetic, studies has emerged indicating that HDL might be associated with the development of other major noncardiovascular diseases, such as infectious disease, autoimmune disease, cancer, type 2 diabetes, kidney disease, and lung disease. In this review, we discuss (1) the association between extreme high HDL cholesterol and mortality and (2) the emerging human evidence linking HDL to several major diseases outside the realm of cardiovascular disease.

Sign in / Sign up

Export Citation Format

Share Document