Basic Research in Cardiology 

About: Basic Research in Cardiology is an academic journal published by Springer Nature. The journal publishes majorly in the area(s): Ischemia & Heart failure. It has an ISSN identifier of 0300-8428. Over the lifetime, 4625 publications have been published receiving 120165 citations.

The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart.

Abstract: A working hypothesis on pathogenesis of ischemic heart damage has been proposed. According to this hypothesis, a crucial role in conversion of reversible damage into irreversible damage is played by cardiomyocyte membrane destruction caused by the so-called “lipid triad”. The latter comprises activation of lipid peroxidation, activation of phospholipases, and the degergentlike action of excessive amounts of free fatty acids and lysophospholipids. Marked activation of lipid peroxidation in experimental myocardial infarction, as well as reoxygenation following transitory ischemia, have been demonstrated. The proposed hypothesis and experimental data underly successful application of synthetic free radical scavengers (antioxidants) for heart protection against experimental myocardial infarction, transitory ischemia, and emotional, painful stress.

Quantitative assessment of myocardial collagen with picrosirius red staining and circularly polarized light.

Abstract: Collagen plays a major role in the structural organization of the heart and therefore direct visualization of collagen fibers is a crucial component of cardiac analysis. Although linearly polarized light has proven an effective tool for the examination of myocardial collagen in histologic sections, the use of circularly polarized light may offer advantages and additional possibilities. We examined the potential enhancement of collagen analysis using circularly polarized light in two ways. We first measured the brightness, and hence indirectly assessed the birefringence, of collagen fibers in scars examined at different times after myocardial infarction. Secondly, we measured collagen content in myocardial tissue and compared results obtained from brightfield analysis of trichrome stained sections with those obtained from circularly polarized light analysis of picrosirius red stained sections. We observed a progressive increase in the maximum brightness of collagen fibers in the scar with time, and a time-dependent shift in the relative distribution of collagen fiber brightness from lower to higher levels. We found consistently lower values of collagen content in trichrome stained versus picrosirius red stained tissue, and concluded that trichrome staining underestimated collagen content. The information provided by these studies could not be obtained by brightfield analysis and could be only partially obtained from linearly polarized light analysis. Thus, analysis using circularly polarized light has the ability to enhance histologic assessment of tissue and can provide additional insights into the composition and structure of myocardial collagen.

Collateral circulation: past and present.

Abstract: Following an arterial occlusion outward remodeling of pre-existent inter-connecting arterioles occurs by proliferation of vascular smooth muscle and endothelial cells. This is initiated by deformation of the endothelial cells through increased pulsatile fluid shear stress (FSS) caused by the steep pressure gradient between the high pre-occlusive and the very low post-occlusive pressure regions that are interconnected by collateral vessels. Shear stress leads to the activation and expression of all NOS isoforms and NO production, followed by endothelial VEGF secretion, which induces MCP-1 synthesis in endothelium and in the smooth muscle of the media. This leads to attraction and activation of monocytes and T-cells into the adventitial space (peripheral collateral vessels) or attachment of these cells to the endothelium (coronary collaterals). Mononuclear cells produce proteases and growth factors to digest the extra-cellular scaffold and allow motility and provide space for the new cells. They also produce NO from iNOS, which is essential for arteriogenesis. The bulk of new tissue production is carried by the smooth muscles of the media, which transform their phenotype from a contractile into a synthetic and proliferative one. Important roles are played by actin binding proteins like ABRA, cofilin, and thymosin beta 4 which determine actin polymerization and maturation. Integrins and connexins are markedly up-regulated. A key role in this concerted action which leads to a 2-to-20 fold increase in vascular diameter, depending on species size (mouse versus human) are the transcription factors AP-1, egr-1, carp, ets, by the Rho pathway and by the Mitogen Activated Kinases ERK-1 and -2. In spite of the enormous increase in tissue mass (up to 50-fold) the degree of functional restoration of blood flow capacity is incomplete and ends at 30% of maximal conductance (coronary) and 40% in the vascular periphery. The process of arteriogenesis can be drastically stimulated by increases in FSS (arterio-venous fistulas) and can be completely blocked by inhibition of NO production, by pharmacological blockade of VEGF-A and by the inhibition of the Rho-pathway. Pharmacological stimulation of arteriogenesis, important for the treatment of arterial occlusive diseases, seems feasible with NO donors.

The role of inflammatory cytokines in endothelial dysfunction

Abstract: Clinical and experimental data support a link between endothelial dysfunction and inflammation. Inflammatory cytokines are important protagonists in formation of atherosclerotic plaque, eliciting effects throughout the atherosclerotic vessel. Importantly, the development of atherosclerotic lesions, regardless of the risk factor, e.g., diabetes, hypertension, obesity, is characterized by disruption in normal function of the endothelial cells. Endothelial cells, which line the internal lumen of the vasculature, are part of a complex system that regulates vasodilation and vasoconstriction, growth of vascular smooth muscle cells, inflammation, and hemostasis, maintaining a proper blood supply to tissues and regulating inflammation and coagulation. Current concepts suggest that the earliest event in atherogenesis is endothelial dysfunction, manifested by deficiencies in the production of nitric oxide (NO) and prostacyclin. The focus of this review is to summarize recent evidence showing the effects of inflammation on vascular dysfunction in ischemic-heart disease, which may prompt new directions for targeting inflammation in future therapies.

Inhibition of permeability transition pore opening by mitochondrial STAT3 and its role in myocardial ischemia/reperfusion

Abstract: The signal transducer and activator of transcription 3 (STAT3) contributes to cardioprotection by ischemic pre- and postconditioning. Mitochondria are central elements of cardioprotective signaling, most likely by delaying mitochondrial permeability transition pore (MPTP) opening, and STAT3 has recently been identified in mitochondria. We now characterized the mitochondrial localization of STAT3 and its impact on respiration and MPTP opening. STAT3 was mainly present in the matrix of subsarcolemmal and interfibrillar cardiomyocyte mitochondria. STAT1, but not STAT5 was also detected in mitochondria under physiological conditions. ADP-stimulated respiration was reduced in mitochondria from mice with a cardiomyocyte-specific deletion of STAT3 (STAT3-KO) versus wildtypes and in rat mitochondria treated with the STAT3 inhibitor Stattic (STAT3 inhibitory compound, 6-Nitrobenzo[b]thiophene 1,1-dioxide). Mitochondria from STAT3-KO mice and Stattic-treated rat mitochondria tolerated less calcium until MPTP opening occurred. STAT3 co-immunoprecipitated with cyclophilin D, the target of the cardioprotective agent and MPTP inhibitor cyclosporine A (CsA). However, CsA reduced infarct size to a similar extent in wildtype and STAT3-KO mice in vivo. Thus, STAT3 possibly contributes to cardioprotection by stimulation of respiration and inhibition of MPTP opening.