| Full text | |
| Author(s): |
Guido, Maria C.
[1]
;
Clemente, Carolina F.
[2]
;
Moretti, Ana I.
;
Barbeiro, Hermes V.
;
Debbas, Victor
[1]
;
Caldini, Elia G.
[3]
;
Franchini, Kleber G.
[2]
;
Soriano, Francisco G.
[4]
Total Authors: 8
|
| Affiliation: | [1] Univ Sao Paulo, Sch Med, Hosp Clin, Inst Heart, BR-01246913 Sao Paulo - Brazil
[2] Univ Estadual Campinas, Sch Med Sci, Dept Internal Med, Campinas, SP - Brazil
[3] Univ Sao Paulo, Sch Med, Dept Pathol, BR-01246913 Sao Paulo - Brazil
[4] Univ Sao Paulo, Fac Med, Lab Disciplina Emergencias Clin, Dept Emergency Med, Sch Med, BR-01246913 Sao Paulo - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Shock; v. 37, n. 1, p. 77-84, JAN 2012. |
| Web of Science Citations: | 5 |
| Abstract | |
Sepsis and septic shock are associated with cardiac depression. Cardiovascular instability is a major cause of death in patients with sepsis. Focal adhesion kinase (FAK) is a potential mediator of cardiomyocyte responses to oxidative and mechanical stress. Myocardial collagen deposition can affect cardiac compliance and contractility. The aim of the present study was to determine whether the silencing of FAK is protective against endotoxemia-induced alterations of cardiac structure and function. In male Wistar rats, endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (10 mg/kg). Cardiac morphometry and function were studied in vivo by left ventricular catheterization and histology. Intravenous injection of small interfering RNA targeting FAK was used to silence myocardial expression of the kinase. The hearts of lipopolysaccharide-injected rats showed collagen deposition, increased matrix metalloproteinase 2 activity, and myocyte hypertrophy, as well as reduced 24-h +dP/dt and -dP/dt, together with hypotension, increased left ventricular end-diastolic pressure, and elevated levels of FAK (phosphorylated and unphosphorylated). Focal adhesion kinase silencing reduced the expression and activation of the kinase in cardiac tissue, as well as protecting against the increased collagen deposition, greater matrix metalloproteinase 2 activity, and reduced cardiac contractility that occur during endotoxemia. In conclusion, FAK is activated in endotoxemia, playing a role in cardiac remodeling and in the impairment of cardiac function. This kinase represents a potential therapeutic target for the protection of cardiac function in patients with sepsis. (AU) | |
| FAPESP's process: | 06/00443-6 - Cardiac remodeling and genic changes induced by LPS: RNAi for terapeuctic use in heart dysfunction |
| Grantee: | Francisco Garcia Soriano |
| Support Opportunities: | Regular Research Grants |