Hypertrophy

Cardiac hypertrophy is the enlargement and thickening of the heart muscle (myocardium) in response to various physiological or pathological stimuli. While it can initially be a compensatory response to increased workload, chronic hypertrophy can lead to adverse structural and functional changes in the heart. The molecular mechanisms underlying cardiac hypertrophy involve signalling pathways that influence gene expression, protein synthesis, and cellular remodelling. Several signalling pathways are known to be critical for regulating cardiac hypertrophy, both physiological (adaptive) and pathological (maladaptive) forms. The calcineurin-NFAT (nuclear factor of activated T cells) pathway is one key mediator of cardiac hypertrophy. Increased intracellular calcium levels activate calcineurin, a phosphatase enzyme which dephosphorylates NFAT (Nuclear Factor of Activated T cells) a transcription factor that plays a crucial role in regulating gene expression. Once dephosphorylated, NFAT translocates to the nucleus, binding to specific DNA sequences (known as NFAT response elements) and activating gene expression programs that contribute to the enlargement of cardiomyocytes and the remodelling of the heart. Although initially adaptive, sustained NFAT activation and hypertrophic signalling can lead to maladaptive hypertrophy, impairing cardiac function and contributing to heart failure. Several MAPK pathways are also implicated in cardiac hypertrophy, including: 1) ERK (Extracellular Signal-Regulated Kinase), which contributes to both physiological and pathological hypertrophy; 2) JNK (c-Jun N-terminal Kinase), associated with maladaptive hypertrophy; and 3) p38 MAPK signalling, which promotes cardiac hypertrophy and contributes to inflammation and fibrosis. The PI3K (Phosphoinositide 3-kinase) - AKT (Protein kinase B) - mTOR (Mechanistic Target of Rapamycin) pathway is also essential for physiological hypertrophy in response to exercise and growth factors. mTOR signalling promotes both increased protein synthesis and ribosome biogenesis, processes necessary for supporting the increased metabolic demand and protein synthesis associated with increased cell growth in hypertrophy. G Protein-Coupled Receptor (GPCR) pathways also play a significant role in cardiac hypertrophy with activation of GPCRs, such as β-adrenergic receptors, leading to intracellular signalling through G proteins, resulting in hypertrophic responses. Physiological hypertrophy can occur in response to exercise or pregnancy, allowing the heart to meet increased demands and involves proportional enlargement of the heart chambers and maintenance of cardiac function. Conversely, pathological hypertrophy often results in concentric hypertrophy, where the heart muscle thickens without a significant increase in chamber size. This adaptation is observed in conditions like hypertension and aortic stenosis, where the heart is pumping against increased resistance. In response to volume overload, as seen in conditions like valvular regurgitation, the heart may undergo eccentric hypertrophy, involving chamber enlargement and increased muscle mass. Cardiac hypertrophy can lead to increased stiffness of the myocardium, impairing its ability to relax during diastole. This reduces filling capacity and can lead to elevated filling pressures, contributing to heart failure with preserved ejection fraction (HFpEF). Finally, hypertrophy also demands increased energy supply due to increased protein synthesis and contractile activity. This can lead to energy imbalances, contributing to subsequent mitochondrial dysfunction and oxidative stress. Altered ion channel expression and calcium handling in hypertrophied hearts may also disrupt normal electrical conduction, potentially leading to arrhythmias. We offer a large product catalogue of research tools for investigating cardiac hypertrophy, including Smad4 antibodies, STAT3 antibodies, ASK1 antibodies, STAT3 ELISA Kits, and IL33 ELISA Kits. Explore our full cardiac hypertrophy product range below and discover more, for less. Alternatively, you can explore our Transcription Factors and Hormones product ranges.