Bone morphogenetic protein-2 − A potential autocrine/paracrine factor in mediating the stretch activated B-type and atrial natriuretic peptide expression in cardiac myocytes

• Mechanical stretch of cultured cardiomyocytes in vitro and in vivo acute or chronic pressure overload, induced by arginine vasopressin or angiotensin II infusion, stimulates cardiac BMP-2 expression, but not BMP-4 expression.
• BMP-2 and -4 increase the mRNA levels of BNP, ANP and GATA-4, and secretion of immunoreactive BNP and ANP resembling the effects of mechanical stretch or hemodynamic overload.
• BMP antagonist Noggin inhibits mechanical stretch or hypertrophic agonist (angiotensin II and phenylephrine) induced natriuretic peptide gene expression.
• Together the results suggest a new role for BMP-2 as a paracrine/autocrine factor that participates in cardiac mechanotransduction and modifies stretch induced hypertrophic response.

Hemodynamic overload exposes the heart to variety of neural, humoral and mechanical stresses. Even without the neurohumoral control of the entire organism cardiac myocytes have the ability to sense mechanical stretch and convert it into adaptive intracellular signals. This process is controlled by several growth factors. Here we show that mechanical stretch in vitro and hemodynamic overload in vivo activated the expression of bone morphogenetic protein-2 (BMP-2), while expression of BMP-4 was temporarily attenuated by stretch. BMP-2 and BMP-4 alone stimulated B-type and atrial natriuretic peptide (BNP and ANP) expression and protein synthesis, and activated transcription factor GATA-4 resembling the effects of mechanical stretch of cultured cardiac myocytes. Further, BMP antagonist Noggin was able to inhibit stretch and hypertrophic agonist induced BNP and ANP expression. Together these data provide evidence for BMP-2 as a new autocrine/paracrine factor that regulates cardiomyocyte mechanotransduction and adaptation to increased mechanical stretch.