Biglcan Is Beneficial In Angiotensin Ii Induced Heart Failure By Preventing Cardiac Inflammation And Remodeling Improving Lv Function And Mortality By Preventing Transdifferentiation Of Myofibroblasts

Biglycan is a small leucine rich proteoglycan and is important for the structural integrity of the extracellular matrix, but also serves as a danger signal and triggers sterile inflammation. Whether biglycan is beneficial or delirious in angiotensin induced heart failure, a model were remodeling as well as inflammation plays a crucial role, is unkown. The present study investigated whether gene deletion of biglycan influences cardiac inflammatory stress response, adverse remodeling as well as apoptosis leading to cardiac dysfunction and mortality after 3 weeks of angiotensin induced heart failure in vivo. Methods and results: Biglycan knockout mice (BGN-/-) and their controls (WT) were subjected to receive angiotensin II (ANGII) or saline for 3 weeks via osmotic mini pump and 21 days later LV function was analyzed invasively. ANGII induced significant cardiac inflammation (increased CD3 (+3.5 fold) and CD11b+ (+5 fold) cells) as well as cardiac dysfunction in WT-ANGII animals. Interestingly, deletion of BGN impaired cardiac function (significantly impaired stroke work, cardiac output and diastolic function) when BGN-/- ANGII were compared to WT-ANGII. This was associated with increased inflammation (CD3, CD11, cytokine expression TNF-alpha) as well as increased collagen accumulation as detrimental LV remolding in BGN-/- ANGII compared to WT-ANGII. This all increased mortality in BGN-/- ANGII (45% vs 0%) in ANGII induced heart failure. Interestingly, we documented an increased number of myofibroblasts in BGN-/- ANGII, which might explain the accumulation of matrix as well as increased inflammatory response compared to WT-ANGII Conclusions: Loss of biglycan increased the inflammatory response, which impaired cardiac remodeling and function during ANGII induced heart failure leading to high mortality in vivo. Therefore, biglycan in ANGII induced heart failure seems to be beneficial by preserving the structural integrity of the matrix and preventing increased transdifferentiation of fibroblasts to myofibroblasts.