Cardiac fibrosis

Li Y, Peng G Li Q, Wen S, Huang TH-W, Roufogalis BD, Yamahara J. (2004) Salacia oblonga improves cardiac fibrosis and inhibits postprandial hyperglycemia in obese zucker rats. Life Sci 75 1735-1746. 

Propazine Negative 450° 15 450 Cardiac fibrosis and focal IRISf1997a... 

Ichihara, S., Senbonmatsu, T., Price, E., Jr., et al. 2001. Angiotensin II type 2 receptor is essential for left ventricular hypertrophy and cardiac fibrosis in chronic angiotensin II-induced hypertension. Circulation 104 346-351. 

Regulatory Role of TGF- 3 in Cardiac Myofibroblast Function and Post-MI Cardiac Fibrosis Key Roles of Smad7 and c-Ski... 

The molecular pathways that couple increased hemodynamic load to cardiac hypertrophy, cardiac fibrosis, and heart failure are multiplex and incompletely understood, despite intense recent investigation (Hunter and Chien 1999 MacLellan and Schneider 2000). Although TGF-pj initiates multiple modes of signal activation, including the recently discovered TPRII/TAK1 pathway (Watkins et al. 2006),... 

Collagen synthesis - Cardiac fibrosis- Heart failure... 

TGF-Px is an Important Ligand in the Context of Heart Failure and in Cardiac Fibrosis... 

The involvement of the c-Ski and C184M in the development of overt cardiac fibrosis and attendant congestive heart failure is unclear. In future studies,... 

Acknowledgments We thank the Heart and Stroke Foundation of Manitoba for their support of this work on Smad7 and c-Ski in the context of cardiac fibrosis and cardiac myofibroblast function. I.M.C.D. is a scholar of the Myles Robinson Heart Health Fund. B.W. was supported by a postdoctoral fellowship of the Manitoba Health Research Council, and both K.M.B. and R.H.C. are supported with operating funds from the Canadian Institutes for Health Research. The authors would also like to thank Mr. Sunil Rattan and Mr. Stephen C. Jones for their technical support in completion of the experimental portion of these studies. 

Wang, B., Hao, J., Jones, S.C., Yee, M.S., Roth, J.C., and Dixon, I.M. 2002. Decreased Smad 7 expression contributes to cardiac fibrosis in the infarcted rat heart. Am. J. Physiol. Heart Circ. Physiol. 282 H1685-H1696. 

Several mechanisms have been postulated to underlie the benefits of aldosterone receptor antagonists in heart failure (30). Aldosterone-induced cardiac fibrosis may reduce systolic function, impair diastolic function, and promote intracardiac conduction defects, with the potential for serious dysrhythmias. Aldosterone may also increase vulnerability to serious dysrhythmias by other mechanisms. The diuretic and hemodynamic effects of spironolactone in RALES and EPHESUS were subtle, and there were no significant changes in body weight, sodium retention, or systemic blood pressure. 

Nitric oxide, endothelium-derived hyperpolarizing factor and prostaglandins Renal and cardiac fibrosis Glomerular function in the IPRK Disadvantages of the IPRK model Advantages of the IPRK model... 

Pi aMHC, WT Cardiac hypertrophy (94,95) T Cardiac fibrosis (94,95) and apoptosis (95) Cardiac dysfunction (94,95) T Intrauterine mortality (75) 4 Inotropic and chronotropic response to ISO (75)... 

The benefits of aldosterone antagonists in heart failure appear to be due largely to their neurohormonal inhibition, namely, inhibition of aldosterone s actions in the heart. Specifically, the benefits are believed to be due to the ability of these agents to inhibit aldosterone-mediated cardiac fibrosis and thus ventricular remodeling. And while spironolactone historically has been viewed as a diuretic, this is believed to contribute little to its benefits in heart failure in part because the doses used have minimal diuretic effect. Thus, as with ACE inhibitors and /S-blockers, the data on aldosterone antagonists also support the neurohormonal model of heart failure. 

Lijnen P, Petrov V. Induction of cardiac fibrosis by aldosterone. J Mol Cell Cardiol 2000 32 865-879. 

Pulmonary fibrosis - dyspnea on exertion Cardiac fibrosis - arrhythmias... 

While profound decreases in SL PLC yi and 8i activities and protein levels occur in CHF, treatment of animals with the ACE inhibitor imidapril partially corrected these changes in PLC isozymes forms as well as cardiac function (Tappia et ah, 1999). This would suggest that RAS may be involved in mediating alterations in PLC isozymes and that PLC isozymes could serve as novel targets for the treatment of CHF. In addition, PLC isozymes could be another target for the mechanisms of action of ACE inhibitors. It is pointed out that an upregulation of the Gqa/PLC-p pathway in the viable, border, and scar tissues in the post-MI hearts is also seen, which may play an important role in cardiac fibrosis and scar remodeling (Ju et ah, 1998). 

Studies also have shown direct effects of aldosterone on the heart and vascular lining aldosterone induces hypertension and interstitial cardiac fibrosis in animal models. The increased cardiac fibrosis is proposed to result from direct mineralocorticoid actions in the heart rather than from the effect of hypertension, because treatment with spironolactone, a MR antagonist, blocks the fibrosis without altering blood pressure. Similar effects of mineralocorticoids on cardiac fibrosis in human beings may explain, at least in part, the beneficial effects of spironolactone in patients with congestive heart failure (see Chapter 33). 

Beare-Rogers and Nera (1972) fed squirrel monkeys (Saimiri sciureus) HEAR oil at 10% and 20% of the diet for 1- and 10-week periods. Each monkey heart was sliced laterally through the apex and the ventral portion was examined histologically. Lipidosis was demonstrated in the hearts of all monkeys at 1 week including those fed the control diet. Lipidosis was still present in one of three monkeys fed HEAR oil at the 10% level and in two of two monkeys fed the same oil at the 20% level at 10 weeks. They reported the presence of cardiac fibrosis in both monkeys fed HEAR oil at 20% for 10 weeks but did not describe the lesions. 

To elucidate the role of a high-fat diet on vascular dysfunction and cardiac fibrosis in the absence of overt obesity and hyperlipidemia, normal female rats were fed a high-fat diet for 8 weeks [37]. This was associated with a modest increase in the body weight and a normal plasma lipid profile. In rats fed a high-fat diet, systolic (171 7mmHg) and diastolic blood pressures (109 3) increased compared to a standard diet (systolic blood pressure, 134 8 diastolic blood pressure,... 

---