ArticleActa pharmacologica Sinica2009
Recombinant adeno-associated virus-mediated human kallikrein gene therapy protects against hypertensive target organ injuries through inhibiting cell apoptosis.
Article in Acta pharmacologica Sinica, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- hKLK alleviates myocardial fibrosis in mice with viral myocarditis.Journal of applied biomedicine · 2023Article
- Good or bad: Application of RAAS inhibitors in COVID-19 patients with cardiovascular comorbidities.Pharmacology & therapeutics · 2020Review
- Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral Vector.Journal of the American Society of Nephrology : JASN · 2018Article
- Cardiac inflammation after local irradiation is influenced by the kallikrein-kinin system.Cancer research · 2012Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
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Abstract
aimOverexpression of human tissue kallikrein (HK), mediated by recombinant adeno-associated virus (rAAV), decreased blood pressure in spontaneous hypertensive rats (SHRs) and reduced injury to the heart, aorta and kidney. In this study, we used both an in vivo animal model and in vitro cell culture system to investigate whether rAAV-mediated HK gene therapy protects against organ damage by inhibiting cell apoptosis.
methodsrAAV encoding HK (rAAV-HK) or LacZ (rAAV-lacZ) were delivered as a control to spontaneously hypertensive rats (SHRs) and cultured human embryonic kidney (HEK) 293 cells.
resultsTreatment with rAAV-HK decreased cell apoptosis in the target organs of SHRs and also inhibited lipopolysaccharide (LPS)-induced HEK 293 apoptosis. The rAAV-HK delivery system also increased the levels of apoptosis-inhibiting proteins bcl-2 and bcl-x(L), and decreased the level of Bax and the activity of caspase 3, two promoters of apoptosis. In addition to its role in the inhibition of apoptosis, rAAV-HK also activated the cell survival and proliferation signaling pathways ERK1/2 and PI3K/AKT.
conclusionrAAV-mediated HK gene delivery has multiple therapeutic possibilities for treating hypertension, not only by decreasing blood pressure, but also by directly inhibiting end-organ damage.
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