Concentric cardiac hypertrophy

Takeishi Y, Ping P, Bolli R, Kirkpatrick DL, Hoit BD, Walsh RA. 2000. Transgenic overexpression of constitutely active protein kinase C-E causes concentric cardiac hypertrophy. Circ Res 86 1218-1223. 

Gq- and phosphatidylinositol 3-kinase-dependent signaling pathways have been linked to the hypertrophic growth of cardiac myocytes. Data highlighting their involvement were reported in numerous in vivo and in vitro studies employing both pharmacological and transgenic approaches. The following section will attempt to summarize their relative role in eccentric and concentric cardiac hypertrophy. 

The Role of PKC and Calcium in Gq-Dependent Induction of Concentric Cardiac Hypertrophy... 

Norepinephrine NE transporter Human cDNA Depression, Alzheimer s disease, epilepsy, anxiety, attention deficit hyperactivity, angina, asthma, cardiac arrhythmia, cardiac hypertrophy, congestive heart failure, myocardial ischemia, hypertension, artherosclerosis, narcolepsy, orthostatic hypotension, prostatic hyperplasia, rhinitis, diabetes, diarrhea, glaucoma, impotence, obesity, opiate withdrawal pain, Raynaud s disease, preterm labor pain Modulation of norepinephrine concentration in the neuronal synaptic clefts, neuroprotection... 

Fig. 12.1 Concentric and eccentric cardiac remodeling. In response to a systolic load, newly formed sarcomeres will be assembled in a parallel fashion leading to an increase in myocyte cell width. This mode of sarcomere assembly will result in a concentric pattern of cardiac hypertrophy characterized by an increase in wall thickness and reduction in chamber volume. In contrast, in response to a diastolic load, newly formed sarcomeres will be assembled in an in series pattern leading to an increase in myocyte cell length. This mode of sarcomere assembly will promote an eccentric pattern of cardiac hypertrophy characterized primarily by an increase in chamber volume. However, a modest increase in wall thickness will also occur because of the secondary increase in systolic wall stress associated with eccentric remodeling.

Pathological cardiac hypertrophy develops in response to stresses, and can be concentric, eccentric, or both. An excess pressure load placed on the heart, for example, resulting from uncorrected hypertension or valvular disease, results in concentric hypertrophy. This hypertrophy is initially believed to be adaptive, normalizing systolic wall stress, though it is not clear that hypertrophy is necessary to maintain systolic function in the face of moderately elevated pressure loads. Eccentric hypertrophy results most often from volume loads such as those in valvular insufficiency. Einally, the hypertrophy that occurs in the remote noninfarcted myocardium, as part of the remodeling process following a myocardial infarction, may be both concentric and eccentric. 

In hyperthyroid rats treated with an ethanol extract equivalent to 400 mg/kg of European bugleweed alone or 10 or 400 mg/kg of European bugleweed with 0.7 mg/kg T4 daily for 56 days, no significant changes of thyroid hormone concentrations or TSH levels were observed. Treatment reduced the increase in heart rate and blood pressure induced by T4 administration, alleviated cardiac hypertrophy, and reduced the density of P-adrenoceptors in heart tissue (Vonhoff et al. 2006). 

The above model was further employed to study observed patterns of cardiac hypertrophy. First, the initial size of the ventricle was consistent with that of a normal dog. Second, a pressure overload was created by raising mean aortic pressure. The model was then used to recompute ventricular size for the new afterload condition. Results show the classic wall thickening and increased wall thickness-to-diameter ratio (W/D), consistent with observed concentric hypertrophy. Third, volume overload was imposed by elevating cardiac output. In this case, the model predicted an increase in diameter with relatively little increase in the W/D ratio, referred to as eccentric hypertrophy. Lastly, the sarcomere function was impaired and its effect on the ventricle evaluated. An eccentric form of hypertrophy resulted. The diameter-to-length... 

Data on the accumulation of 22 1 fatty acids in humans are also available from the work of Svaar who examined autopsy material from 54 hearts selected from Norwegian men, age 20 to 69, who had died suddenly from accidents (Svaar, 1982). These hearts were selected from a larger group on the basis of being without myocardial infarction, severe coronary stenosis, cardiac hypertrophy or valvular disease by macroscopical examination. No focal myocardial lesions were present. A mild to moderate lipidosis was found in 50% of the hearts but this was not correlated with the concentration of 22 1 which was present at less than 1% of the total lipids (Svaar,... 

Ideally, a biomarker of cardiac hypertrophy would be predictive, that is, its concentration in serum or plasma would be altered in advance of eventual increases in heart weight, and specific for the heart in both humans and animals commonly used in safety assessment. This would allow early detection of cardiac risk in short-duration toxicology studies (e.g., l days), serial monitoring in longer-duration toxicology studies, or pharmacology studies in order to enable the prediction of cardiac hypertrophy liabilities in humans. In practice, biomarkers are not always specific for a certain organ or... 

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