Actin-myosin Interaction Research Articles

Shortening-Induced Force Depression in Single Sarcomeres is Abolished by MgADP-Activation

The mechanisms behind the shortening-induced force depression (FD) commonly observed in skeletal muscles remain unclear, but have been associated with sarcomere length non-uniformity and/or cross-bridge inhibition. The purpose of this study was twofold: (i) to evaluate if FD is present in isolated single sarcomeres, a preparation that eliminates sarcomere length non-uniformities and (ii) to evaluate if FD is inhibited when single sarcomeres are activated with MgADP, which biases cross-bridges into a strongly-bound state. Single sarcomeres (n=16) were isolated from rabbit psoas myofibrils using two micro-needles (one compliant, one rigid), piercing the sarcomere externally adjacent to the Z-lines. The sarcomeres were contracted isometrically and subsequently shortened, in both Ca2+- and MgADP-activating solutions. Shortening in Ca2+-activated samples resulted in a 27.44% ± 9.04% force depression when compared to isometric contractions produced at similar final sarcomere lengths (P > 0.001). There was no FD in MgADP-activated sarcomeres (FD = −1.79% ± 9.69%, P = 0.435). These results suggest that FD is a sarcomeric property, and that is associated with an inhibition of myosin-actin interactions.

Evaluation of the Effect of Glyceraldehyde 3-phosphate Dehydrogenase on Heat-induced Myofibril Gels by Investigating Actin-myosin Interaction

Evaluation of the Effect of Glyceraldehyde 3-phosphate Dehydrogenase on Heat-induced Myofibril Gels by Investigating Actin-myosin Interaction

Altered myocardial force generation in end‐stage human heart failure

This study aimed to elucidate the molecular background of increased Ca2+ sensitivity of force production in cardiomyocytes of end-stage human heart failure. Ca2+ -activated isometric force and the cross-bridge specific rate of force redevelopment (ktr ) were determined in Triton-skinned myocytes from end-stage failing and non-failing donor hearts. Measurements (control: pH 7.2, 0 mM inorganic phosphate (Pi )) were performed under test conditions that probed either the Ca2+ -regulatory function of the thin filaments (pH 6.5), the kinetics of the actin-myosin cross-bridge cycle (10 mM Pi ), or both (pH 6.5, 10 mM Pi ). The control maximal Ca2+ -activated force (Fo ) and ktrmax did not differ between failing and non-failing myocytes. At submaximal [Ca2+ ], however, both force and ktr were higher in failing than in donor myocytes. The difference in the Ca2+ sensitivities of force production was preserved when the thin filament regulatory function was perturbed by acidosis (pH 6.5) but was abolished by cross-bridge modulation (i.e. by Pi ) both at pH 7.2 and at pH 6.5. Pi induced a larger reduction in force but a smaller increase in ktr in the failing myocytes than in the non-failing myocytes at submaximal [Ca2+ ]. The enhanced Pi sensitivity of the actin-myosin interaction suggests that the Pi release step of the actin-myosin cross-bridge cycle is modified during end-stage human heart failure. This might be of functional importance when Pi accumulates (e.g. during cardiac ischaemia). Moreover, this alteration can influence cardiac energetics and the clinical efficacy of sarcomere targeted agents in human heart failure.

Non-crossbridge forces in activated striated muscles: a titin dependent mechanism of regulation?

When skeletal muscles are stretched during activation in the absence of myosin-actin interactions, the force increases significantly. The force remains elevated throughout the activation period. The mechanism behind this non-crossbridge force, referred to as static tension, is unknown and generates debate in the literature. It has been suggested that the static tension is caused by Ca(2+)-induced changes in the properties of titin molecules that happens during activation and stretch, but a comprehensive evaluation of such possibility is still lacking. This paper reviews the general characteristics of the static tension, and evaluates the proposed mechanism by which titin may change the force upon stretch. Evidence is presented suggesting that an increase in intracellular Ca(2+) concentration leads to Ca(2+) binding to the PEVK region of titin. Such binding increases titin stiffness, which increases the overall sarcomere stiffness and causes the static tension. If this form of Ca(2+)-induced increase in titin stiffness is confirmed in future studies, it may have large implications for understating of the basic mechanisms of muscle contraction.

The immediate effect of HCM causing actin mutants E99K and A230V on actin–Tm–myosin interaction in thin-filament reconstituted myocardium

Human cardiac actin mutants E99K and A230V were expressed with baculovirus/insect cells and used to reconstitute the thin-filament of bovine cardiac (BVC) muscle fibers, together with tropomyosin (Tm) and troponin (Tn) purified from bovine ventricles. Effects of [Ca2+], [ATP], and [phosphate] on tension and its transients were studied at 25°C. In the absence of Tm/Tn, both mutants significantly decreased the tension of actin filament reconstituted fibers (WT: 0.75±0.06 T0, E99K: 0.58±0.04 T0, A230V: 0.58±0.03 T0), where T0 is active tension of native fibers (T0=26.9±1.1kPa, N=41), indicating diminished actin–myosin interactions. However, in the presence of Tm and Tn, WT, E99K, and A230V recovered tension (0.85±0.06 T0, 0.89±0.06 T0, and 0.85±0.05 T0, respectively), demonstrating the compensatory effect of Tm/Tn. Ca2+ sensitivity (pCa50) increased (5.59±0.02, 5.80±0.03, 5.77±0.03, respectively) and cooperativity (nH) decreased (2.6±0.3, 1.87±0.21, 1.60±0.11, respectively). The kinetic constants of the cross-bridge cycle were deduced using sinusoidal analysis. E99K did not show any significant changes in any of the kinetic constants compared to those of WT. A230V caused a decrease in K1 (ATP association constant), k2 and k−2 (rate constants of the cross-bridge detachment step). The cross-bridge distribution was similar among WT, E99K, and A230V. In conclusion, our experiments demonstrate that the first step of HCM pathogenesis with E99K is increased pCa50 and decreased nH, which result in larger tension during partial activation to cause a diastolic problem. The effect on nH is more severe with A230V. In addition, A230V has a problem of decreased cross-bridge kinetics, which affects the normal functions of the cross-bridge cycle and may contribute to the first step of the HCM pathogenesis.

Degradation of cardiac myosin light chain kinase by matrix metalloproteinase-2 contributes to myocardial contractile dysfunction during ischemia/reperfusion

Although ischemia/reperfusion (I/R)-induced myocardial contractile dysfunction is associated with a prominent decrease in myofilament Ca2+ sensitivity, the underlying mechanisms have not yet been fully clarified. Phosphorylation of ventricular myosin light chain 2 (MLC-2v) facilitates actin–myosin interactions and enhances contractility, however, its level and regulation by cardiac MLC kinase (cMLCK) and cMLC phosphatase (cMLCP) in I/R hearts are debatable. In this study, the levels and/or effects of MLC-2v phosphorylation, cMLCK, cMLCP, and proteases during I/R were determined. Global myocardial I/R-suppressed cardiac performance in isolated rat hearts was concomitant with decreases of MLC-2v phosphorylation, myofibrillar Ca2+-stimulated ATPase activity, and cMLCK content, but not cMLCP proteins. Consistently, simulated I/R in isolated cardiomyocytes inhibited cell shortening, Ca2+ transients, MLC-2v phosphorylation, and myofilament sensitivity to Ca2+. These observations were reversed by cMLCK overexpression, while the specific cMLCK knockdown by short hairpin RNA (shRNA) had the opposite effect. Moreover, the inhibition of matrix metalloproteinase-2 (MMP-2, a zinc-dependent endopeptidase) reversed IR-decreased cMLCK, MLC-2v phosphorylation, myofibrillar Ca2+-stimulated ATPase activity, myocardial contractile function, and myofilament sensitivity to Ca2+, while the inhibition or knockdown of cMLCK by ML-9 or specific shRNA abolished MMP-2 inhibition-induced cardioprotection. Finally, the co-localization in cardiomyocytes and interaction in vivo of MMP-2 and cMLCK were observed. Purified recombinant rat cMLCK was concentration- and time-dependently degraded by rat MMP-2 in vitro, and this was prevented by the inhibition of MMP-2. These findings reveal that the I/R-activated MMP-2 leads to the degradation of cMLCK, resulting in a reduction of MLC-2v phosphorylation, and myofibrillar Ca2+-stimulated ATPase activity, which subsequently suppresses myocardial contractile function through a decrease of myofilament Ca2+ sensitivity.

Dynamic F-actin movement is essential for fertilization in Arabidopsis thaliana

In animals, microtubules and centrosomes direct the migration of gamete pronuclei for fertilization. By contrast, flowering plants have lost essential components of the centrosome, raising the question of how flowering plants control gamete nuclei migration during fertilization. Here, we use Arabidopsis thaliana to document a novel mechanism that regulates F-actin dynamics in the female gametes and is essential for fertilization. Live imaging shows that F-actin structures assist the male nucleus during its migration towards the female nucleus. We identify a female gamete-specific Rho-GTPase that regulates F-actin dynamics and further show that actin-myosin interactions are also involved in male gamete nucleus migration. Genetic analyses and imaging indicate that microtubules are dispensable for migration and fusion of male and female gamete nuclei. The innovation of a novel actin-based mechanism of fertilization during plant evolution might account for the complete loss of the centrosome in flowering plants.

Changes in Some Biochemical Indices of Stability of Broiler Chicken Actomyosin at Different Levels of Sodium Bicarbonate in Presence and Absence of Sodium Chloride

This study examined some physicochemical properties of actomyosin isolated from pre-rigor chicken breast muscle (Pectoralis major) to gain insight on its interaction with 0.2–1.0M sodium bicarbonate (NaHCO3) either with or without 3% sodium chloride (NaCl). NaHCO3 has been a frequent quality raiser with respect to water holding capacity of meat, which is adversely affected at low pH. This study document a remarkable inactivation of ATPases and the weakening of actin-myosin interaction with increasing molarity of NaHCO3, irrespective of the presence or absence of NaCl. Similarly, there was a concomitant increase in turbidity of soluble fraction, increase in total protein solubility and reactive SH groups. The observations on protein solubility/insolubility are supported by SDS-PAGE profiles. Therefore, the conformational changes induced by NaHCO3 are concentration dependent and appear different from those during thermal transitions. The findings suggest that low concentration of NaHCO3 may be more suitable component of marinades, since it affects the main myofibrillar contractile complex less adversely.

A simple kinetic model of myocardium contraction: Calcium-mechanics coupling

A kinetic model of cardiac muscle contraction is suggested. It is based on our earlier simplified model of the kinetics of the actin-myosin interaction. We examined the kinetics of formation of calcium-troponin complexes which open the binding sites on actin for myosin heads. The model also takes into account the cooperativity of this process and the influence of myosin heads on it. It was shown that with proper choice of its parameters the model appropriately describes the dependence of myocardium activation on sarcomeres length that underlies the Frank-Starling law of the heart. The model fits both steady-state experiments on myocardial specimens with permeable membrane and twitch contractions of intact cardiac muscle. It also describes well the myocardium load-dependent relaxation.

Mammary stem cells have myoepithelial cell properties.

Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy.

Regulation of structure and function of sarcomeric actin filaments in striated muscle of the nematode Caenorhabditis elegans.

The nematode Caenorhabditis elegans has been used as a valuable system to study structure and function of striated muscle. The body wall muscle of C. elegans is obliquely striated muscle with highly organized sarcomeric assembly of actin, myosin, and other accessory proteins. Genetic and molecular biological studies in C. elegans have identified a number of genes encoding structural and regulatory components for the muscle contractile apparatuses, and many of them have counterparts in mammalian cardiac and skeletal muscles or striated muscles in other invertebrates. Applicability of genetics, cell biology, and biochemistry has made C. elegans an excellent system to study mechanisms of muscle contractility and assembly and maintenance of myofibrils. This review focuses on the regulatory mechanisms of structure and function of actin filaments in the C. elegans body wall muscle. Sarcomeric actin filaments in C. elegans muscle are associated with the troponin-tropomyosin system that regulates the actin-myosin interaction. Proteins that bind to the side and ends of actin filaments support ordered assembly of thin filaments. Furthermore, regulators of actin dynamics play important roles in initial assembly, growth, and maintenance of sarcomeres. The knowledge acquired in C. elegans can serve as bases to understand the basic mechanisms of muscle structure and function.

The Kinetics Underlying the Velocity of Smooth Muscle Myosin Filament Sliding on Actin Filaments in Vitro

Actin-myosin interactions are well studied using soluble myosin fragments, but little is known about effects of myosin filament structure on mechanochemistry. We stabilized unphosphorylated smooth muscle myosin (SMM) and phosphorylated smooth muscle myosin (pSMM) filaments against ATP-induced depolymerization using a cross-linker and attached fluorescent rhodamine (XL-Rh-SMM). Electron micrographs showed that these side polar filaments are very similar to unmodified filaments. They are ~0.63 μm long and contain ~176 molecules. Rate constants for ATP-induced dissociation and ADP release from acto-myosin for filaments and S1 heads were similar. Actin-activated ATPases of SMM and XL-Rh-SMM were similarly regulated. XL-Rh-pSMM filaments moved processively on F-actin that was bound to a PEG brush surface. ATP dependence of filament velocities was similar to that for solution ATPases at high [actin], suggesting that both processes are limited by the same kinetic step (weak to strong transition) and therefore are attachment- limited. This differs from actin sliding over myosin monomers, which is primarily detachment-limited. Fitting filament data to an attachment-limited model showed that approximately half of the heads are available to move the filament, consistent with a side polar structure. We suggest the low stiffness subfragment 2 (S2) domain remains unhindered during filament motion in our assay. Actin-bound negatively displaced heads will impart minimal drag force because of S2 buckling. Given the ADP release rate, the velocity, and the length of S2, these heads will detach from actin before slack is taken up into a backwardly displaced high stiffness position. This mechanism explains the lack of detachment- limited kinetics at physiological [ATP]. These findings address how nonlinear elasticity in assemblies of motors leads to efficient collective force generation.

The path to visualization of walking myosin V by high-speed atomic force microscopy.

The quest for understanding the mechanism of myosin-based motility started with studies on muscle contraction. From numerous studies, the basic frameworks for this mechanism were constructed and brilliant hypotheses were put forward. However, the argument about the most crucial issue of how the actin–myosin interaction generates contractile force and shortening has not been definitive. To increase the “directness of measurement”, in vitro motility assays and single-molecule optical techniques were created and used. Consequently, detailed knowledge of the motility of muscle myosin evolved, which resulted in provoking more arguments to a higher level. In parallel with technical progress, advances in cell biology led to the discovery of many classes of myosins. Myosin V was discovered to be a processive motor, unlike myosin II. The processivity reduced experimental difficulties because it allowed continuous tracing of the motor action of single myosin V molecules. Extensive studies of myosin V were expected to resolve arguments and build a consensus but did not necessarily do so. The directness of measurement was further enhanced by the recent advent of high-speed atomic force microscopy capable of directly visualizing biological molecules in action at high spatiotemporal resolution. This microscopy clearly visualized myosin V molecules walking on actin filaments and at last provided irrefutable evidence for the swinging lever-arm motion propelling the molecules. However, a peculiar foot stomp behavior also appeared in the AFM movie, raising new questions of the chemo-mechanical coupling in this motor and myosin motors in general. This article reviews these changes in the research of myosin motility and proposes new ideas to resolve the newly raised questions.

Sequence of a complete chicken BG haplotype shows dynamic expansion and contraction of two gene lineages with particular expression patterns.

Many genes important in immunity are found as multigene families. The butyrophilin genes are members of the B7 family, playing diverse roles in co-regulation and perhaps in antigen presentation. In humans, a fixed number of butyrophilin genes are found in and around the major histocompatibility complex (MHC), and show striking association with particular autoimmune diseases. In chickens, BG genes encode homologues with somewhat different domain organisation. Only a few BG genes have been characterised, one involved in actin-myosin interaction in the intestinal brush border, and another implicated in resistance to viral diseases. We characterise all BG genes in B12 chickens, finding a multigene family organised as tandem repeats in the BG region outside the MHC, a single gene in the MHC (the BF-BL region), and another single gene on a different chromosome. There is a precise cell and tissue expression for each gene, but overall there are two kinds, those expressed by haemopoietic cells and those expressed in tissues (presumably non-haemopoietic cells), correlating with two different kinds of promoters and 5′ untranslated regions (5′UTR). However, the multigene family in the BG region contains many hybrid genes, suggesting recombination and/or deletion as major evolutionary forces. We identify BG genes in the chicken whole genome shotgun sequence, as well as by comparison to other haplotypes by fibre fluorescence in situ hybridisation, confirming dynamic expansion and contraction within the BG region. Thus, the BG genes in chickens are undergoing much more rapid evolution compared to their homologues in mammals, for reasons yet to be understood.

Hypoxic pulmonary hypertension: the paradigm is changing.

Hypoxic pulmonary hypertension: the paradigm is changing.

Coupling of lever arm swing and biased Brownian motion in actomyosin.

An important unresolved problem associated with actomyosin motors is the role of Brownian motion in the process of force generation. On the basis of structural observations of myosins and actins, the widely held lever-arm hypothesis has been proposed, in which proteins are assumed to show sequential structural changes among observed and hypothesized structures to exert mechanical force. An alternative hypothesis, the Brownian motion hypothesis, has been supported by single-molecule experiments and emphasizes more on the roles of fluctuating protein movement. In this study, we address the long-standing controversy between the lever-arm hypothesis and the Brownian motion hypothesis through in silico observations of an actomyosin system. We study a system composed of myosin II and actin filament by calculating free-energy landscapes of actin-myosin interactions using the molecular dynamics method and by simulating transitions among dynamically changing free-energy landscapes using the Monte Carlo method. The results obtained by this combined multi-scale calculation show that myosin with inorganic phosphate (Pi) and ADP weakly binds to actin and that after releasing Pi and ADP, myosin moves along the actin filament toward the strong-binding site by exhibiting the biased Brownian motion, a behavior consistent with the observed single-molecular behavior of myosin. Conformational flexibility of loops at the actin-interface of myosin and the N-terminus of actin subunit is necessary for the distinct bias in the Brownian motion. Both the 5.5–11 nm displacement due to the biased Brownian motion and the 3–5 nm displacement due to lever-arm swing contribute to the net displacement of myosin. The calculated results further suggest that the recovery stroke of the lever arm plays an important role in enhancing the displacement of myosin through multiple cycles of ATP hydrolysis, suggesting a unified movement mechanism for various members of the myosin family.

Combined troponin I Ser-150 and Ser-23/24 phosphorylation sustains thin filament Ca2 + sensitivity and accelerates deactivation in an acidic environment

The binding of Ca2+ to troponin C (TnC) in the troponin complex is a critical step regulating the thin filament, the actin–myosin interaction and cardiac contraction. Phosphorylation of the troponin complex is a key regulatory mechanism to match cardiac contraction to demand. Here we demonstrate that phosphorylation of the troponin I (TnI) subunit is simultaneously increased at Ser-150 and Ser-23/24 during in vivo myocardial ischemia. Myocardial ischemia decreases intracellular pH resulting in depressed binding of Ca2+ to TnC and impaired contraction. To determine the pathological relevance of these simultaneous TnI phosphorylations we measured individual TnI Ser-150 (S150D), Ser-23/24 (S23/24D) and combined (S23/24/150D) pseudo-phosphorylation effects on thin filament regulation at acidic pH similar to that in myocardial ischemia. Results demonstrate that while acidic pH decreased thin filament Ca2+ binding to TnC regardless of TnI composition, TnI S150D attenuated this decrease rendering it similar to non-phosphorylated TnI at normal pH. The dissociation of Ca2+ from TnC was unaltered by pH such that TnI S150D remained slow, S23/24D remained accelerated and the combined S23/24/150D remained accelerated. This effect of the combined TnI Ser-150 and Ser-23/24 pseudo-phosphorylations to maintain Ca2+ binding while accelerating Ca2+ dissociation represents the first post-translational modification of troponin by phosphorylation to both accelerate thin filament deactivation and maintain Ca2+ sensitive activation. These data suggest that TnI Ser-150 phosphorylation induced attenuation of the pH-dependent decrease in Ca2+ sensitivity and its combination with Ser-23/24 phosphorylation to maintain accelerated thin filament deactivation may impart an adaptive role to preserve contraction during acidic ischemia pH without slowing relaxation.

Quality properties of pre- and post-rigor beef muscle after interventions with high frequency ultrasound

The delivery of a consistent quality product to the consumer is vitally important for the food industry. The aim of this study was to investigate the potential for using high frequency ultrasound applied to pre- and post-rigor beef muscle on the metabolism and subsequent quality. High frequency ultrasound (600kHz at 48kPa and 65kPa acoustic pressure) applied to post-rigor beef striploin steaks resulted in no significant effect on the texture (peak force value) of cooked steaks as measured by a Tenderometer. There was no added benefit of ultrasound treatment above that of the normal ageing process after ageing of the steaks for 7days at 4°C. Ultrasound treatment of post-rigor beef steaks resulted in a darkening of fresh steaks but after ageing for 7days at 4°C, the ultrasound-treated steaks were similar in colour to that of the aged, untreated steaks. High frequency ultrasound (2MHz at 48kPa acoustic pressure) applied to pre-rigor beef neck muscle had no effect on the pH, but the calculated exhaustion factor suggested that there was some effect on metabolism and actin-myosin interaction. However, the resultant texture of cooked, ultrasound-treated muscle was lower in tenderness compared to the control sample. After ageing for 3weeks at 0°C, the ultrasound-treated samples had the same peak force value as the control. High frequency ultrasound had no significant effect on the colour parameters of pre-rigor beef neck muscle. This proof-of-concept study showed no effect of ultrasound on quality but did indicate that the application of high frequency ultrasound to pre-rigor beef muscle shows potential for modifying ATP turnover and further investigation is warranted.

Structural and functional effects of two stabilizing substitutions, D137L and G126R, in the middle part of α‐tropomyosin molecule

Tropomyosin (Tm) is an α-helical coiled-coil protein that binds along the length of actin filament and plays an essential role in the regulation of muscle contraction. There are two highly conserved non-canonical residues in the middle part of the Tm molecule, Asp137 and Gly126, which are thought to impart conformational instability (flexibility) to this region of Tm which is considered crucial for its regulatory functions. It was shown previously that replacement of these residues by canonical ones (Leu substitution for Asp137 and Arg substitution for Gly126) results in stabilization of the coiled-coil in the middle of Tm and affects its regulatory function. Here we employed various methods to compare structural and functional features of Tm mutants carrying stabilizing substitutions Arg137Leu and Gly126Arg. Moreover, we for the first time analyzed the properties of Tm carrying both these substitutions within the same molecule. The results show that both substitutions similarly stabilize the Tm coiled-coil structure, and their combined action leads to further significant stabilization of the Tm molecule. This stabilization not only enhances maximal sliding velocity of regulated actin filaments in the in vitro motility assay at high Ca(2+) concentrations but also increases Ca(2+) sensitivity of the actin-myosin interaction underlying this sliding. We propose that the effects of these substitutions on the Ca(2+)-regulated actin-myosin interaction can be accounted for not only by decreased flexibility of actin-bound Tm but also by their influence on the interactions between the middle part of Tm and certain sites of the myosin head.

Hypertrophic Cardiomyopathy with Familial Chylomicronemia Syndrome: Is it an Incidental Finding or a New Association?

To the Editor: Familial chylomicronemia syndrome (FCS) iscausedbygeneticdeficiencyoflipoprotein lipase(LPL)oritscofactor apo C II characterized by the presence of chylomi-crons and a marked increase in plasma triglyceride levels thatfrequently manifests duringinfancy orchildhood withaprev-alence of 1/1,000,000 [1–3]. We present an infant diagnosedas FCS associated with hypertrophic cardiomyopathy (HCM)who has improved with diet and high dose omega-3 therapyduring follow up. To our current knowledge, this associationhas not been reported before.One-mo-old boy was admitted to hospital because ofinvestigation for hyperlipidemia, as his brother was be-ing followed with FCS. His parents were consanguine-ous. The triglyceride and cholesterol levels were 38500/15000 mg/dL. Genetic analysis identified a homozygotemutation (c.644 G>A) in LPL gene. Echocardiographyshowed the prominent biventricular HCM (Fig. 1a andb). The increase in the interventricular septum thicknessand hyperechogenicity of all myocardial walls were alsonoted. A fat restricted diet involving formula withmedium-chain tryglycerides (MCT) was started. Afterthe sixth month, complementary feeding and MCT oilwere added. High dose omega-3 (3×1,000 mg) wasgiven. After 2 y follow-up, the lipid levels were mea-sured between 1,500 and 2,000 mg/dL and HCM re-solved (Fig. 1c).Cardiologic complications occur in these patients but theHCM is an unexpected finding with FCS. The differentialdiagnosisofHCMincludesDanonorFabrydiseases.Ventric-ular hypertrophy in these conditions is not accompanied bymyocyte disarrayor fibrosis but by a characteristic accumula-tion of glycogen or glycosphingolipids in cellular vacuoles[4]. In our patient, clearance of very high chylomicrons byLPL was impairedand this caused anabnormal accumulationin the heart. Early diet treatment and omega-3 supplementa-tion seems to be effective in the lowering of TG levels.The importance of inherited molecular mechanismsincludingincreasedactin-activatedATPaseactivity,disruptionof actin-myosin interaction have been recognized in thepathogenesis of cardiomyopathy [5]. In our case, we thinkthat FCS resulted a reversible lipid deposition within themyocardium.